Hep B Blog

Category Archives: Hepatitis B Treatment

Gilead Lead Chronic HepB Candidate GS-9620 Conceived as a More Patient-Friendly Interferon

Harnessing the Power of RNAi Gene Silencing in a 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. 

As I was reading the latest PK-PD study by Gilead on its lead experimental chronic HepB drug candidate GS-9620 (Fosdick et al. 2013), it finally dawned on me that much-touted GS-9620 has been designed to be nothing more than a better tolerated, more convenient version of an already existing treatment option, recombinant interferon.  GS-9620 is therefore an example of the typical incrementalist Big Pharma value creation strategy.  By contrast, if successful, an HBsAg knockdown approach such as with Arrowhead’s ARC520 would bring to healthcare providers and patients an entirely new, desperately needed treatment option as the field has become stuck with interferons and RT inhibitors for years.  Continue reading "Gilead Lead Chronic HepB Candidate GS-9620 Conceived as a More Patient-Friendly Interferon"

HBV Journal Review – November 2013

HBF 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:

  • Patients Who Clear Hepatitis B During Antiviral Treatment Do Well Long-Term
  • However, the Prognosis is Poor for Most Who Stop Antiviral Treatment
  • How Effective Are Antivirals in Reducing Cirrhosis and Preventing Liver Cancer?
  • New Antiviral Besifovir Hampered by Carnitine Deficiency in Early Clinical Trial
  • Liver Cancer Remains Major Health Threat, with Few Treatment Options
  • Scientists Develop a Better Mouse for Hepatitis B and C Research
  • HBV-Infected People Have a Higher Risk of Rheumatoid Arthritis
  • Ear Wax May Transmit Hepatitis B
  • Children with Frequent Ear Infections Do Not Respond as Well to Vaccines
  • Clean-Shave Haircuts Leave Traces of Virus on the Scalp  Continue reading "HBV Journal Review – November 2013"

ISIS/GSK and Tekmira Come Out with HBV Knockdown Plans

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. 

If you did not appreciate the value the pharmaceutical industry has come to place on the HBsAg knockdown concept for achieving a functional cure for chronic Hepatitis B (HBV) infection, the last two days will have woken you up.

Yesterday, ISIS Pharmaceuticals reported that it had received a $7M milestone payment related to the development of an antiviral RNaseH development candidate (ISIS-GSK3Rx, aka ISIS-HBVRx) which, although undisclosed for competitive reasons, has got to be for HBV.  And today, Tekmira publicly announced that they will file an IND for an HBV-RNAi candidate in 2014 while hinting at the partnering potential of such a treatment candidate.

Arrowhead Research is thus not alone in their efforts any more.  Coincidentally, Arrowhead reported today the completion of their enrollment of the phase I single-dose, healthy volunteer study with ARC520, their DPC-delivered candidate for chronic HBV.  Accordingly, the dose escalation was able to run through all the pre-planned 6 dose cohorts up to the top dose of 2.0mg/kg.

Apparently, there were no signs of significant dose-related toxicities.  The only finding of concern among the 36 volunteers, 24 of which received drug, was 2 cases of lightheadedness of uncertain clinical relevance.  As these occurred at the highest dose, it seems that the company suspects that it could have been drug-related although the study remains blinded for follow-up.

A dose of 2mg/kg without any serious adverse events or dose-limiting toxicities is a great start for DPC delivery technology.  This is especially the case when one considers that the single-molecule subQ version of DPC that I hope will form the basis for the upcoming pipeline candidates, except for the next one perhaps, will be much more potent than the two-molecule version of intravenously delivered ARC520 based on the non-human primate data presented at last year’s OTS meeting.

With 2mg/kg of ARC520, I further believe that HBsAg knockdowns of over 90% are likely.  The biggest challenge going forward with this program will be setting a knockdown goal and getting the dose and dose frequency right.

 

HBV Journal Review – October 2013

HBF 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:

  • Study Finds Only 21% of Hepatitis B Patients Are Treated Correctly
  • Combination of Chinese Herbs Plus Antiviral Entecavir Proves Effective
  • Caesarians Reduce Infection of Newborns When Mothers Have High Viral Loads
  • Combined Antiviral and Interferon Treatment Effective in Those Under Age 30
  • New Tenofovir Formula May Lead to Less Bone Loss and Kidney Problems
  • HBV Mutation Found Only in Men May Explain Their Higher Rates of Liver Damage
  • Sumo Wrestlers Found to Transmit HBV Infection
  • Taiwan’s Hepatitis B Immunization of Infants Reduces Hepatitis B by 90%
  • Tenofovir Reverses Severe, Decompensated Cirrhosis

HBV Journal Review
October 1, 2013
Volume 10, Issue 10
by Christine M. Kukka 

Study Finds Only 21% of Hepatitis B Patients Are Treated Correctly

A new study, examining how well San Francisco primary care providers care for their patients infected with the hepatitis B virus (HBV), finds most fail to screen them for liver cancer or regularly evaluate their viral load or hepatitis B “e” antigen (HBeAg) status, though medical guidelines require annual or semi-annual testing.

The study, published in the September 2013 issue of the journal Digestive Diseases and Sciences, surveyed doctors who provide care through a safety net program to many uninsured patients. They were asked how well they thought they followed current medical guidelines, and then patient medical records were analyzed to assess the true quality of care.

Of the 148 doctors surveyed, 79% claimed to follow medical guidelines and monitor patients’ liver health every 6 six 12 months. However, patient medical records covering the last 12 months showed substandard care.

  • • Only 75% of patients had their alanine aminotransferase (ALT) levels, which shows liver damage, tested in the past year.
  • • Only 51% had their viral load (HBV DNA) tested.
  • • Only 51% had been screened for liver cancer (either with an alpha fetoprotein test or some type of liver imaging). This test should be performed annually, and doctors are at risk of medical malpractice if they do not screen patients for cancer.
  • • HBeAg tests were performed in only 29% of patients.
  • • Only 32% of the hepatitis B patients had been immunized against hepatitis A, another guideline requirement, to protect them from another liver infection.

Bottom line, researchers found that only 21% of patients had been monitored properly in compliance with current hepatitis B guidelines. Forty-three percent of doctors were not familiar with medical guidelines for hepatitis B management and only 73% answered all questions about hepatitis B correctly.

There was also a racial bias regarding which HBV-infected patients were screened for hepatitis C and HIV. Doctors tended to test African-American and Latino patients for hepatitis C (48% and 44% respectively) at a higher rate than they tested whites and Asian-American patients (34% and 31%.)

The study suggests that fear of malpractice—more than knowledge of current practice guidelines—may drive doctors to perform the required liver cancer screenings each year. Also, the researchers suggest that hepatitis B public education initiatives, spearheaded by the San Francisco Hepatitis B Free Campaign, may have contributed to better monitoring of Asian-Americans because it raised awareness among the public and their providers.

“These findings highlight the importance of targeted provider education to improve overall care,” for hepatitis B, the researchers from the University of California, San Francisco, suggest.

Continue reading about this and additional HBV related studies

HBV Journal Review – September 2013

HBF 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:

  • 39.2% of U.S. Newborns Aren’t Getting Hepatitis B Vaccine at Birth
  • Researchers Suggest Banning or Restricting Lamivudine to Avoid Drug Resistance
  • Knowledge Gap About Hepatitis B Persists Among Asian-Americans
  • Even Liver Specialists Fail to Immunize Patients Against Viral Hepatitis
  • Many Seek Viral Hepatitis Tests Only When Symptoms Appear
  • After Six Years of Tenofovir Treatment, Still No Signs of Drug Resistance
  • More Studies Examine Link Between Vitamin D and Liver Damage
  • Study Examines Which Hepatitis B Patients Relapse with Chemotherapy
  • Interferon Treatment May Cause Some Hearing Loss
  • African-Americans Suffer the Highest Rates of New HBV Infections in the U.S.

HBV Journal Review
September 1, 2013
Volume 10, Issue 8
by Christine M. Kukka 

 

 39.2% of U.S. Newborns Aren’t Getting Hepatitis B Vaccine at Birth

Which newborns aren’t getting immunized against hepatitis B in the U.S.? The infants who:

  • • Do not have health insurance
  • • Live in states without a universal hepatitis B vaccine supply policy
  • • And have only one provider who administered vaccines.

According to a U.S. Centers for Disease Control and Prevention study, published in the August issue of the journal Preventive Medicine, an alarming 39.2% of newborns missed the first, critical birth dose of hepatitis B vaccination that can protect newborns from hepatitis B even if their mothers are infected.

These results come from data analysis of the 2009 National Immunization Survey of 17,053 U.S. children, aged 19-35 months.

“Children who reside in states without a universal hepatitis B vaccine supply policy, and are not covered by health insurance are two important modifiable risk factors for not receiving the birth dose hepatitis B vaccination, future intervention studies could be needed to help control those modifiable risk factors,” CDC researchers wrote.

Source: www.ncbi.nlm.nih.gov/pubmed/23988497

Researchers Suggest Banning or Restricting Lamivudine to Avoid Drug Resistance
A global team of researchers suggest lamivudine (Epivir-HBV) never be used to treat hepatitis B patients because it frequently leads to drug resistance and sets the stage for resistance to other antivirals, such as entecavir (Baraclude).

Lamivudine, the first antiviral approved for hepatitis B treatment, has fallen out of favor in North America and Europe because of its high rate of drug resistance. But because of its low cost, it continues to be commonly used to treat hepatitis B virus (HBV) infection in Asia and Africa, where the majority of the world’s hepatitis B patients live.

This report, published in the July 30 issue of PLoS One, examined the molecular make-up of the virus in many patients who had been treated with lamivudine as well as patients who had never been treated. They found the many untreated patients carry a mutation that allows HBV to quickly mutate and develop resistance to lamivudine.

“Our findings strongly suggest that the use of lamivudine will not benefit …patients,” they wrote because of the high risk of lamivudine resistance.

“Finally, since patients can quickly develop drug resistance to entecavir in the presence of lamivudine mutations, the lamivudine mutations can significantly compromise the efficacy of entecavir,” they concluded.

They proposed that doctor screen patients for these mutations before ever prescribing lamivudine,”… to most effectively treat chronic hepatitis B patients by selecting only sensitive drugs.” …

Continue reading about this and additional HBV related studies

Diagnosed With Chronic Hepatitis B? What Phase – Immune Clearance?

In the last chronic hepatitis B stages blog, we looked at the immune tolerant phase.

At some point the immune system recognizes the hepatitis B virus and the chronically infected person will enter a phase referred to as the immune clearance ( also know as the immune active, or immune reactive HBeAg–positive phase). During this phase blood work will show that you are HBeAg positive, with lower levels of HBV DNA when compared to the immune tolerant stage, and increased ALT levels. (Remember, it is not at all unusual for kids to have viral loads in the millions or even billions.) During this “clearance” phase the immune system is actively attacking infected liver cells. This is both good and bad. On the good side, if the immune system is able to “beat” the virus, the person will go through HBeAg seroconversion and lose the HBeAg antigen. This means that HBeAg will go from positive to negative and the HBeAb antibody, or anti-HBe will go from negative to positive.  This results in significant decrease in the hepatitis B virus level, often to an undetectable level, and normalization of ALT and other liver function labs. Successful HBe serconversion moves you into the inactive HBsAg carrier phase.

When the immune system activates and starts attacking infected liver cells, it not only kills the virus, but also the host liver-cells. You probably won’t feel any of this, but your ALT (SGPT) and AST (SGOT) lab values will be elevated. These enzymes are released when there is inflammation caused by liver cells that are injured or killed.  Your doctor may see a mild, moderate or high levels of ALT elevation reflecting damage done in the liver. Ultimately the problem is how much liver damage occurs during the process of HBeAg seroconversion?

It is possible a person will quickly and spontaneously move into and out of the immune clearance phase, and with a limited amount of liver damage. However, some people may cycle for years with intermittent flares, which are evidenced by ALT elevations which may be as high as 10 times above the upper limits of normal (normal is 30 IU/mL for men and 19 IU/mL for women) when clearance is attempted.  While the immune system attacks infected liver cells, viral replication will decrease and ALT levels will elevate as infected liver cells die in the battle.  If successful, the immune system response will result in HBe seroconversion –  losing HBeAg, gaining the HBe antibody, decline of the virus to very low or undetectable levels, and normalization of ALT/AST levels.

Unfortunately that might not be enough, and the immune system may not be able to put up a big enough fight permitting HBe seroconversion. Evidence of this are ALT levels that go back down, and viral replication that goes back up. (Note the above diagram.) This cycling up and down over time will be reflected in lab work if a liver specialist monitors you regularly. If you are not having your ALT levels regularly monitored (every few months), then you may miss these cycles of intermittent flares over time. It is during these flares that liver damage occurs, and you will likely be completely unaware, unless you have lab work done during a flare, or you wait until there are symptoms and significant liver damage.

It is during the immune clearance phase when treatment is typically recommended. It is true that a chronically infected person will eventually serconvert HBe spontaneously – without treatment, but most liver specialists choose to treat in order to prevent years of flares and damage to the liver.

Next time, next stage … Inactive Carrier, Reversion, or HBe Mutation?

HBV Journal Review – August 2013

HBF 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:

*First Clinical Trial Using “RNA Interference” for Hepatitis B Begins
*Why Do Some People Clear HBsAg After Years of Chronic Infection?
*Longer Antiviral Treatment Urged after Seroconversion to Prevent Relapse
*Federal Officials Dramatically Undercount Liver Disease Deaths in the U.S.
*More Women Than Men Retain Protection Against Hepatitis B After
*Immunization Hepatitis B Cirrhosis Declines in China, But Alcohol-related
*Cirrhosis Rises Hepatitis E Vaccine Development Shows Promise
*Tenofovir Most Effective Antiviral Treatment in HIV-HBV Coinfected Patients
*Study Confirms Coffee Protects the Liver in European Populations
*Hepatitis C Is Also a Risk for Southeast Asians, Including Women
*In Small Trial, Chinese Herbal Medicine Reduces ALT Levels

HBV Journal Review
August 1, 2013
Volume 10, Issue 8
by Christine M. Kukka

First Clinical Trial Using “RNA Interference” for Hepatitis B Begins

A ground-breaking approach to hepatitis B treatment, which manipulates RNA messengers to halt viral replication, has begun its first human clinical trial. If successful, this approach would be a paradigm shift in treatment, possibly re- placing interferon and antivirals.

In animal trials, reported in the May 2013 journal Molecular Therapy, RNA interference (RNAi) treatment reduced hepatitis B surface antigen (HBsAg) levels to undetectable within 24 hours in mice and the antigen remained undetectable for nearly a month.

RNAi treatment works by destroying or “silencing” the molecular messengers that carry im- portant genetic information to the hepatitis B virus (HBV) antigen/ protein factories. Without the critical information that messenger RNA molecules carry, these antigen factories shut down and HBV reproduction de- clines dramatically.

Early RNAi research found that RNA silencing worked extremely well in the liver, but the challenge has been to create a formula and delivery system to target hepatitis B antigens in liver cells without affecting other important cells.

Arrowhead Research Corp. found that when the small RNA interrupters are linked to cholesterol, they target liver cells extremely well, and the addition of special polymers helps the gene silencing process. Arrowhead designed an intravenous formula, called ARC-520, that is utilized in its Phase 1 trial.

The hope is that when the viral load is dramatically reduced, the body’s immune system can gain the upper hand and eradicate the infection on its own.

In addition to its mouse trial, a similar trial involving an HBV infected chimp with an extremely high viral load also led to rapid reduction in HBV DNA and a 90% reduction in another hepatitis B antigen—the hepatitis B “e” antigen (HBeAg).

The clinical trial of ARC-520 (which uses a Dynamic Polyconju- gate delivery platform and includes two distinct RNA silencing agents that should shut down hepatitis B anti- gen reproduction) in humans is taking place in Melbourne, Australia. It is a randomized, double-blind, placebo- controlled trial. Each group of six healthy volunteers will receive either a placebo intra- venous injection or a single dose of ARC- 520…
Continue reading about this and additional studies…

 

HBV Journal Review – July 2013

HBF 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 Describe When to Treat Pregnant Women with Antivirals
Does pregnancy worsen hepatitis B?
When should pregnant women be treated?
Which antivirals are safe to use during pregnancy?
What if women have elevated ALTs before becoming pregnant and have never         been treated?
What about women with normal ALTs and high viral loads?
Is it safe to use antivirals during the entire pregnancy?
Monitoring recommendations after delivery
Can a woman taking antivirals breastfeed?
* Half of Patients Treated Long-Term with Tenofovir Lose HBeAg
*Even Patients with High Viral Load Lose HBeAg with Tenofovir
*New Type of Interferon Effective in Phase 2 Hepatitis B Trial
*Majority of Hepatitis B Patients Have Vitamin D Deficiency
*But Patients with Healthy Vitamin D Levels Are More Likely to Clear HBsAg
*Activists Develop a National Plan to Eradicate Hepatitis B in the U.S.
*New Guidelines Urge Britain’s Doctors to Improve Hepatitis B Care
*Measuring HBsAg Levels May Identify Fibrosis and Avoid Liver Biopsies
*HBsAg Levels May Also Predict Cancer Risk in HBeAg-negative Patients

HBV Journal Review


July 1, 2013, Vol 10, no 7
by Christine M. Kukka

Experts Describe When to Treat Pregnant Women with Antivirals
Two U.S. hepatitis B experts have crafted guidelines for doctors to use when deciding when to treat pregnant women infected with the hepatitis B virus (HBV) with antivirals in order to safeguard the women’s health and prevent infection of newborns.

More than half of new hepatitis B infections result from mother-to-child (vertical) transmission and despite immediate immunization and administration of HBIG (hepatitis antibodies), about 30% of infants born to women with high viral loads become infected. Additionally, women who want to become pregnant may already be treated with antivirals because of liver damage.  There is little medical guidance on whether treatment is safe over the entire pregnancy.

Does pregnancy worsen hepatitis B? Generally it does not unless the woman has cirrhosis (severe liver scarring.) Studies show a pregnant woman’s viral load generally does not increase over a pregnancy, but after the baby is born and the woman’s hormone levels change (akin to a sudden decline in steroids), some women experience a “flare” and their alanine transaminase (ALT) levels may increase due to moderate liver cell damage. Because of these flares, doctors must monitor new mothers carefully for several weeks after childbirth.

When should pregnant women be treated? Starting in the second or third trimester of pregnancy, antiviral treatment is recommended when women have high viral loads—exceeding 1 million copies per milliliter or 200,000 international units per milliliter. However, if women are already receiving antiviral treatment when they become pregnant, treatment should probably continue over the pregnancy to prevent worsening liver disease.

Which antivirals are safe to use during pregnancy? The experts recommend tenofovir (Viread) in the event the woman continues to need antiviral treatment because this drug has a very low rate of drug resistance, or telbivudine (Tyzeka). Both have been shown to be safe and cause no birth defects when used in pregnant women infected with HIV or HBV.

Continue reading about this and additional studies…


High HBV Viral Load Tied to Low Serum Vitamin D Levels

An interesting study published in Healio Hepatology:  “High HBV viral load tied to low serum vitamin D levels” discusses the relationship between the HBV viral load and vitamin D levels. In fact is shows seasonal fluctuations of HBV viral load associated with vitamin D levels. Vitamin D has been on the radar for years, but this interesting correlation between HBV virus flucuations and vitamin D levels warrants additional research to investigate how adequate vitamin D levels can positively impact treatment for those living with chronic HBV. Please refer to earlier blogs, Hepatitis B and Vitamin D and Got HBV? Adding Vitamin D to Your Diet for additional information.  As always, please talk to your doctor and have your serum vitamin D levels checked before making any drastic changes to your diet or supplements you may be taking. Don’t forget that vitamin D is the sunshine vitamin, so be sure to keep in mind the impact of the seasons on your levels. 

Patients with chronic hepatitis B who also were vitamin D deficient had significantly higher HBV DNA levels than patients with adequate vitamin D concentrations in a recent study.

In a retrospective study, researchers measured the serum levels of 25-hydroxyvitamin D (25OHD) in 203 treatment-naive patients with chronic hepatitis B seen between January 2009 and December 2012. Patients with 25OHD levels less than10 ng/mL were considered severely deficient, levels below 20 ng/mL were considered deficient, and levels of 20 ng/mL or greater were considered adequate. Patients’ samples were collected upon initial presentation, except 29 participants whose samples were taken at antiviral therapy initiation.

The mean 25OHD concentration for the cohort was 14.4 ng/mL. Forty-seven percent of participants were considered 25OHD deficient; 34% were severely deficient. 25OHD levels were similar between Caucasians (14.38 ng/mL) and non-Caucasians (14.59 ng/mL) (P=.7).

An inverse correlation was observed between levels of HBV DNA and 25OHD (P=.0003). Multivariate analysis indicated that HBV DNA was strongly predictive of low 25OHD levels (P=.000048), and vice versa (P=.0013). Patients with HBV DNA levels less than 2,000 IU/mL had 25OHD concentrations of 17 ng/mL; those with 2,000 IU/mL or higher had concentrations of 11 ng/mL (P<.00001 for difference). Participants who tested positive for hepatitis B e antigen (HBeAg; n=26) had significantly lower 25OHD levels than HBeAg-negative participants (P=.0013); this association was significant only under univariate analysis.

Investigators also noted fluctuations in HBV DNA and 25OHD levels according to season. Significantly lower HBV DNA levels were observed among samples taken during spring or summer than in autumn or winter (P=.01).

“The present study demonstrates a profound association between higher levels of HBV replication and low [25OHD] serum levels in chronic hepatitis B patients,” the researchers wrote. “At least in patients without advanced liver disease … HBV DNA viral load appears to be the strongest determinant of low [25OHD] serum levels. … Future studies to evaluate a therapeutic value of vitamin D and its analogs in HBV infection may be justified.”

HBV Journal Review – June 2013

HBF 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:

• U.S. Doctors Failing to Treat Patients Who Need Treatment
• Doctors Say Poor Training and Limited Resources Contribute to
Substandard Care • More Proof—Many Patients with Slightly Elevated ALTs
Have Fibrosis • Tenofovir Reduces Viral Load in HBeAg-Positive Patients
Faster than Entecavir • Researchers Find Tenofovir Does Not Damage
Kidneys • Tenofovir and Entecavir Highly Effective—If Taken as
Prescribed • Family History of Liver Cancer Boosts Cancer Risk to 15.8%
Among HBV-Infected • Vitamin D Deficiencies Found in People with High
Viral Loads • More Evidence Shows Breastfeeding Does Not Transmit HBV
Infection • Cesareans Do Not Reduce Mother-to-Child HBV Infection
• 2% of HBV Genotype D Adults Lose HBsAg Annually

HBV Journal Review

June 1, 2013, Vol 10, no 6
by Christine M. Kukka

U.S. Doctors Failing to Treat Patients Who Need Treatment
Fewer than 50% of patients infected with the hepatitis B virus (HBV) who need treatment get antivirals or interferon from their primary care doctors and fewer than 70% of patients who go to university liver clinics get appropriate treatment, according to research presented at the Digestive Disease Week medical conference held in Orlando in May.

Stanford University researchers conducted a real-life study to see what percentage of 1,976 hepatitis B patients treated in various clinical settings over four years received treatment. They used current medical guidelines when evaluating whether patients received appropriate treatment.

Continue reading about this and additional studies…