Friday, June 22, 2012

Hepatitis Weekly Rewind- HCV Interferon Free Future? Plus News and Research

I just returned home from a wonderful week of sand and sunshine with my daughter and two grandchildren. As you might imagine Friday came all to quickly for this grandmum. I already miss their little excited faces hovering over my own at 6:00 am -  asking if the coyote we saw last night is outside our door this morning, waiting to eat them!

I quickly reassured my four year old grandson with; "Coyotes never leave the forest before noon, and besides they only eat children with green teeth." After twenty minutes of screams and hysteria, we all brushed our teeth. The downside? My grandchildren now refuse to eat anything green. I so understand. 

As this week comes to a close we take a look back at the most relevant HCV headlines, including today's news with updates as the day progresses. Click here to view previous "HCV  Weekly Rewind" articles.

IDX184 in combination with pegylated interferon and ribavirin

We begin with the pharmaceutical company Idenix and their experimental nucleotide inhibitor IDX184.  The company announced data from the mid-stage study this week showing that all patients  taking a high dose of the drug cleared the virus in four weeks after treatment was completed and 80 % of participants that took a lower dose achieved the same results.

From (Reuters) ;

The drug, IDX184, was given to 31 patients in combination with the standard hep C treatments pegylated interferon and ribavirin.

Nine patients received the combination therapy for 12 extended weeks and were checked four weeks later for signs of the virus in the blood to determine if there was a sustained virologic response, or SVR.

All four patients in the 100 mg arm and four out of five patients in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment.

Patients who did not have undetectable levels of virus at 4 weeks and 12 weeks automatically entered the 36-week combination therapy extended treatment phase which is ongoing, the company said.

FYI -  Investing commentary

Dig a little deeper and you'll see there's a little more to the story.
First, between both doses, there are only nine patients. Hepatitis C drugs tend to perform fairly consistently as trials progress, so solid early data shouldn't be dismissed. With just nine patients, though, it isn't clear whether the data will be closer to 80% -- a ho-hum result -- or 100%, which would obviously be very competitive.

More important, those nine patients were from a subset of patients that responded well to the initial treatment with a combination of IDX184, pegylated interferon, and ribavirin. Of the 31 patients that entered the trial, only 18 had undetectable virus levels four weeks and 12 weeks after treatment. Nine of those patients were given 12 additional weeks of pegylated interferon and ribavirin, which is the interim data we have now. The other nine were given the combo for an additional 36 weeks.

Presumably those patients that stay on the drugs for 36 weeks will perform as well or better than those that were given the drugs for just 12 weeks. But what about the 13 patients that weren't randomized to get either 12 or 36 weeks of additional treatment? One achieved a quick response like the other 18, but dropped out of the study before the randomization began. The other 12 didn't achieve a quick response and were put on the longer 36-week treatment, so it isn't known how many will eventually come up positive. Keep in mind that group represents 40% of those known to still be enrolled in the trial, which could drag down the overall cure rate.

Not that the combo of IDX184, pegylated interferon, and ribavirin will ever see the light of day. Pegylated interferons -- Roche's Pegasys and Merck's (NYS: MRK) PegIntron -- have to be injected and have nasty side effects. Idenix ran this trial simply to gauge IDX184's efficacy, which seems fairly good for now, but it'll need to combine it with (an)other oral drug(s) to compete with all oral regimens being developed by Gilead Sciences (NAS: GILD) , Bristol-Myers Squibb (NYS: BMY) , Abbott Labs (NYS: ABT) , and others.

Which drug(s)? Management didn't say.

It likely depends on who owns IDX184. If Bristol's BMS-986094, which it got from the acquisition of Inhibitex, is a failure -- hints of that here -- the pharma might be interested in picking up IDX184 to combine with its daclatasvir, which has already been shown to work well with Gilead's nucleotide inhibitor.

If Idenix has to go it alone, the biotech has an NS5A inhibitor, same class as daclatasvir, a little behind IDX184. That seems like a less than ideal scenario for investors, but certainly an option if no one is interested in picking up IDX184 or the whole company.

 Read more here....

Over at Pharmalot Ed Silverman discusses resistance to HCV medications, in particular Bristol-Myers Squibb and the altered protocol in their clinical trial for daclatasvir.

According to, the drugmaker changed the protocol to its COMMAND-3 trial, which compares its drug in combination with interferon and ribavirin to Incivek, a protease inhibitor sold by Vertex Pharmaceuticals, along with interferon and ribavarin. What was the change? Bristol-Myers restricted future enrollment to patients who have only genotype 1b HCV, rather than all genotype 1 patients (see this and this)......

Continue Reading @ Pharmalot

Dr David Suhy on using ddRNAi to develop a therapeutic for hepatitis C
A video was released a few days ago by Tacere Therapeutics, Inc., with Dr David Suhy discussing the companies program to bring a triple ddRNAi cassette to clinical trial, click here to view the video.

European regulators investigating drug-safety reporting at Roche
The European Medicines Agency announced Thursday that it is working with national medicines agencies to investigate deficiencies in drug-safety reporting by Roche, including whether the issues may have an impact on the overall benefit-risk profile for any of the products involved. The regulator noted that "there is at present no evidence of a negative impact for patients and while the investigations are being conducted there is no need for patients or healthcare professionals to take any action."
Continue reading here....


New @ NATAP - Interferon Free Future ?

Recent Successes and Noteworthy Future Prospects in the Treatment of Chronic Hepatitis C: TOWARD AN INTERFERON-FREE FUTURE?
"proof of the concept that HCV infection can be cured without interferon" ......"undetectable HCV RNA 4 weeks after end of treatment in 44 of 44 genotype 1 treatment-naive patients with 24 weeks of total therapy.......SVR 12 exceeding 90% over 40 genotype 1 treatment-naive patients"..."SVR 12 exceeding 90% over 40 genotype 1 treatment-naive patients" with 12 weeks therapy
CID supplement July 15 2012 "The Evolving Paradigm of Hepatitis C"

Continue reading....

Global Burden of Hepatitis C: Considerations for Healthcare Providers in the United States
Hepatitis C continues to cause substantial morbidity and mortality worldwide, and transmission continues unabated in many countries. Control of HCV infection requires a comprehensive approach that incorporates primary prevention of transmission through enhanced infection control and injection safety in healthcare settings and in the community, universal screening of blood and blood products, harm reduction programs, and increased public awareness about risk factors for HCV infection. For the 130-170 million persons already infected, newer, more effective therapies are available. However, lack of access to screening, care, and treatment limit the use of these therapies for most persons living with HCV infection globally, and deaths from preventable cirrhosis and liver cancer continue to increase. Governments need to address viral hepatitis comprehensively by improving surveillance, prevention, care, and treatment. In the United States, healthcare providers must be cognizant of the global burden and epidemiology of HCV infection and follow current screening care and treatment recommendations. In addition, they should consider screening foreign-born patients as appropriate, particularly those from countries where HCV infection is highly endemic, who may not have recognized risk factors for HCV infection...Continue reading...

Hepatitis C Virus and the Infectious Diseases Community
It is a perfect storm for the chronic viral infection associated with the greatest morbidity and mortality in the United States. Of the ≥3 million Americans infected with hepatitis C virus (HCV), only ≤50% know they are infected. Infections acquired many years ago from parenteral exposures-injection drug use, transfusions received before screening assay availability (in 1992), or other healthcare exposures-have either no or nonspecific (but highly prevalent) symptoms, such as fatigue, arthritis, and depression. Clinicians tend to discount the extrahepatic effects of HCV infection, although HCV has been associated with diabetes and other serious morbidities. Now, after latencies of 20-30 years, there are rapidly increasing cases of cirrhosis, end-stage liver disease, hepatocellular carcinoma, and early deaths in the Baby Boom generation. The traditional bulwark for viral hepatitis care has been a small number of board-certified hepatologists-only about 2000-who are now overwhelmed. Although many never studied HCV in medical school, infectious disease and general clinicians are being called on for diagnosis and care for a rapidly increasing number of patients. In conjunction with World Hepatitis Day (28 July), this is an appropriate time to provide an overview of where we are and the immediate future for control and treatment of the HCV epidemic.
Continue reading............

New @ HIV and Hepatitis

HBV Genotype Affects Hepatitis B Disease Progression and Outcomes
Friday, 22 June 2012 00:00 Written by Liz Highleyman

Hepatitis B virus (HBV) genotype influences long-term outcomes including viral clearance, according to a Swedish study reported in the May 18, 2012, advance edition of the Journal of Clinical Virology. Genotype C in particular appears to be associated with more aggressive disease. 
It is well known that genotype is a major determinant of treatment response for people with hepatitis C, although it does not seem to have much influence on disease severity. In contrast, the influence of genotype in people with hepatitis B is not well understood...
Continue reading...

From the Pipeline: a Promising New Treatment for HIV and Hepatitis C

Created on 22 June 2012 Written by David Miller Category: Noteworthy

Approximately 4-5 million people worldwide are known to be co-infected with HIV and Hepatitis C (HCV). Managing HCV could be made easier by treating it with the same medication used for HIV. BIT-225 is one such treatment and is being studied for both illnesses.

Shown at the International Conference on Antiviral Research (ICAR) this April in Sapporo, Japan, BIT-225 is a VPU inhibitor in development by Biotron, a small Australia-based biotechnology company. Accumulating research from various institutions and researchers has highlighted the importance of VPU in HIV production.

 VPU is an HIV accessory protein involved in the release of viral particles. All of the available HIV drugs target a step of the HIV lifecycle, preventing the virus from doing its job and thus stopping HIV from continuing to infect cells. For example, nucleoside analogs and non- nucleoside analogs target nucleoside reverse transcriptase and protease inhibitors target the protease enzyme.

VPU helps with the assembly of new virus particles, assisting them to bud from the infected cell. Without VPU, HIV remains attached to the surface of the human cell in which it has replicated. It is possible for HIV to replicate and bud without this particular protein, but only 10% or 20% as many new virus particles are produced. Without the VPU gene, the virus actually kills off the infected cell quicker, delaying the cytopathic (cell-killing) effects of infection that keeps the cell alive slightly longer so that it can produce more virus particles.

The goal of BIT-225 is to gain entry into cell reservoirs where current ARV’s cannot. This would allow the drug to kill off infected cells in reservoirs while other ARV’s prevent the spread of active virus. Penetrating reservoirs is a strategy that many feel is among the best options for curing HIV.
Recent results from a study of BIT-225 show the VPU inhibitor to be promising for the treatment of HCV. An HIV trial is also currently underway and another planned for this year in people co-infected with HIV and HCV.

In a Phase IIa trial, BIT 225 was used in combination with interferon and ribavirin (standard treatment). The drug was given to 24 people for four weeks. The participants were then followed for an additional 44 weeks while they took interferon and ribavirin. Participants received either 200 or 400 mg. of BIT-225 along with interferon and ribavirin, with a third group given interferon, ribavirin and placebo.

At the end of the 4 weeks, eighty-seven percent of people in the 400 mg. arm had an undetectable viral load compared to sixty-three percent of people who received interferon and ribavirin with a placebo. An additional 1 log decrease in HCV viral load was seen in study participants who added BIT 225 to interferon and ribavirin.

Follow-up data at 12 weeks showed the viral decrease was sustained two months after BIT 225 was stopped. Those who participated in this study had a HCV- 1, the most common genotype in the U.S., Europe and South America. Additional follow-up data is expected to be presented in the second half of 2012.

A phase Ia/IIb clinical trial is scheduled to begin dosing in June, with results expected later this year. BIT 225 will be given to 24 HIV treatment naive people in Bangkok, the same clinic where the HCV trial was conducted.

A Phase IIa study is planned for mid 2012 of BIT 225 in people with HIV and HCV co-infection. The study will be extended to include HCV-2 and HCV-3.

An abstract published today at GastroHep from the June issue of Aliment Pharmacol Ther 2012: 36(2): 104–114 offers data on the IL-28B genotype as a predictor of SVR in HCV geno1 patients receiving peginterferon (pegIFN) and ribavirin.

Polymorphisms are a strong predictor of sustained virologic response in HCV genotype 1 patients
The most recent issue of the Alimentary Pharmacology & Therapeutics investigates polymorphisms in the IL-28B genotype and sustained viral clearance in HCV genotype 1 patients.

Polymorphisms in the IL-28B region are a strong predictor of sustained virologic response in individual studies of HCV genotype 1 patients receiving peginterferon (pegIFN) and ribavirin.

Dr Rangnekar and Fontana from Michigan, USA obtained a pooled odds ratio of sustained virologic response in patients of varying race with the favourable IL-28B genotype compared to those with the unfavourable genotype.

A literature search was conducted using online databases and a review of conference abstracts.

The association of the IL-28B genotype with sustained virologic response was similar in all 3 racial groups
Alimentary Pharmacology & Therapeutics

A random effects meta-analysis was performed and study heterogeneity and publication bias were assessed.

There were 21 individual studies of HCV genotype 1 patients of varying ethnicity treated with pegIFN and ribavirin.

The pooled prevalence of the favourable IL-28B genotype varied by race.

However, the strength of association of the IL-28B genotype with sustained virologic response was similar in all 3 racial groups.

The researchers found that IL-28B genotype was also associated with sustained virologic response in 263 HIV/HCV co-infected Caucasians.

The team observed that study quality score and anti-viral treatment regimen did not impact the strength of the association in patient subgroups nor in the pooled population.

Dr Rangnekar's concludes, "IL-28B genotype is significantly associated with sustained virologic response in HCV genotype 1 patients of varying race, as well as in HIV co-infected patients, receiving pegIFN and ribavirin."

"IL-28B testing in conjunction with other pre-treatment parameters may prove useful in counselling HCV patients."

Case reports in gastroenterology
Published: June 2012

A Patient with Chronic Hepatitis C and a Pancreatic Mass in Endoscopic Ultrasound
Mehdi Ghobakhlou, Amir Houshang Mohammad Alizadeh, Nosratollah Naderi, Shirin Haghighi, Mahsa Molaei, Mitra Rafiezadeh, Mohammad Reza Zali

Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran, Iran
Download Full PDF Here...

We report a rare case of pancreas tumor (lymphoma) in a patient with a history of chronic hepatitis C virus (HCV) infection without treatment, with a high viral load (20,199,805 IU/ml). He presented with abdominal pain, jaundice, weight loss and sweating. Computed tomography showed a hypodense mass located in the head of the pancreas, and immunohistochemistry of a specimen obtained by endoscopic ultrasound-guided fine needle aspiration revealed non-Hodgkin’s lymphoma of the pancreas, B cell type. An association of HCV infection with pancreatic lymphoma has only been reported rarely in the literature and its clinical significance is uncertain..full text available here

Interferon responses and spontaneous HCV clearance: Is it all a matter of fat?
As with many provocative studies, the work by Sheridan and colleagues may have raised more questions than it answers but it is certainly a valuable contribution. These data offer some potential explanations to some puzzling aspects of the complicated but slowly emerging picture of HCV, lipids and interferon responses. The possibility that interferon non-response is related to effects on lipids is certainly intriguing and merits further study and exploration of the potential relevance for spontaneous HCV clearance, may be even more important...Continue reading...

New Guidelines for the Diagnosis, Management of Non-Alcoholic Fatty Liver Disease
INDIANAPOLIS -- June 21, 2012 -- New guidelines for diagnosis and management of non-alcoholic fatty liver disease (NAFLD) have been developed and are published in the June issues of the journals Hepatology, Gastroenterology, and the American Journal of Gastroenterology.

This is the first time practice guidelines have been developed for the condition by the 3 major medical societies: the American Association for the Study of Liver Diseases, the American College of Gastroenterology, and the American Gastroenterological Association.

"Although the condition has been recognised for 100 years, because of the increasing frequency of obesity, diabetes and metabolic syndrome, the prevalence and incidence of non-alcoholic fatty liver disease is rapidly becoming the most common cause of cirrhosis in the United States," said Naga P. Chalasani, MD, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana.

The new guideline offers recommendations for evaluation of incidentally discovered hepatic steatosis; recommendations for screening in primary care, diabetes, and obesity clinics; recommendations non-invasive assessment of steatohepatitis and advanced fibrosis in NAFLD; when to obtain a liver biopsy in patients with NAFLD; management of patients with NAFLD, including lifestyle interventions, treatment with metformin and thiazolidinediones, as well nutritional supplements such as ursodeoxycholic aid and omega-3 fatty acids.

The guideline also covers topics such bariatric surgery and statin use in this patient population.

Aspects of NAFLD specific to children and adolescents are also covered, including prevalence, risk factors, and recommendations for screening children for NAFLD.

The full guideline can be found here:

SOURCE: Indiana University School of Medicine

Alcoholic cirrhosis and the risk of hepatocellular carcinoma

This week Medpage today published a CME on a Danish study showing that patients with alcoholic cirrhosis have a lower risk of liver cancer than previously thought.

In a Danish registry study, 5-year risk of hepatocellular carcinoma among these patients was only 1%, Peter Jepsen, MD, PhD, of Aarhus University Hospital, and colleagues reported in the June 19 issue of the Annals of Internal Medicine.
And liver cancer contributed little to the high mortality seen in this population overall, as only 1.8% of deaths were related to the carcinoma, they found. 
As a result, "hepatocellular carcinoma surveillance would be expected to have a minimal effect on mortality and is unlikely to be cost-effective," they wrote. 
Patients with alcoholic cirrhosis are at higher risk for hepatocellular carcinoma than the general population, but the utility of liver cancer surveillance for these patients is unclear. 
Jepsen and colleagues looked at data from a national registry on hepatocellular carcinoma among 8,482 Danish patients who'd been diagnosed with alcoholic cirrhosis between 1993 and 2005. Median follow-up was 4.1 years. 
Over the study period, 169 patients developed hepatocellular carcinoma. 
The researchers found that cumulative risk of the cancer increased steadily with time since the cirrhosis diagnosis, and was 1% at 5 years (95% CI 0.8% to 1.3%). 
In sensitivity analyses that included all possible hepatocellular carcinoma diagnoses and a subpopulation of patients who were followed by hepatologists, the highest 5-year cancer risk was not much higher, at only 1.9%. 
Cancer incidence was markedly higher for men than for women, they reported, and it rose with age. 
Most of the patients who developed the cancer died (151 of 169), and 83.5% of these deaths were related to the cancer. The median survival time from diagnosis was 97 days for localized disease and 37 days for metastatic disease. 
Overall mortality was high in the cohort, with 67.6% of patients dying during the study period.
In an assessment of cause-specific mortality through Jan. 1, 2009, the cumulative 5-year total mortality was 43.5%, while the 5-year risk for hepatocellular carcinoma death was only 0.8%, the researchers reported. 
Thus, only 1.8% of all deaths were liver cancer-related -- a proportion that didn't change noticeably over time, they wrote. 
"Hepatocellular carcinoma contributes little to their high mortality," Jepsen and colleagues wrote, noting that the results suggest cirrhosis patients would benefit only marginally from routine liver cancer surveillance, which falls below the country's accepted threshold for cost-effectiveness anyway. 
They noted that the study was limited because diagnoses of cirrhosis and hepatocellular carcinoma were made by hospital physicians without uniform clinical criteria, and because the registry data lacked detailed information on patient care.
Continue reading here....

Vaccination- hepatitis B

(Reuters Health) reported vaccination against hepatitis B seems to protect against the virus for 25 years, suggesting booster shots are unnecessary, according to a new study from Taiwan.

SOURCE: Journal of Hepatology, online June 4, 2012, continue reading here.

Hepatitis C outbreak at Exeter Hospital - 20 people have tested positive

In the news today 44 victims seek a class-action lawsuit in the hepatitis C outbreak.

By Aaron Sanborn

Earlier this week the Feds became involved in the investigation

The U.S. attorney’s office has joined the investigation into the hepatitis C outbreak at Exeter Hospital’s cardiac catheterization lab.
State public health officials have said they suspect a lab employee’s misuse of drugs led to the outbreak. A hospital worker and 19 of the lab’s patients have tested positive for the liver-destroying disease since the investigation began last month.

U.S. Attorney John Kacavas said Tuesday that his office has brought in personnel from the Food and Drug Administration and FBI to determine whether the outbreak is a criminal or civil matter.

In the meantime, a Concord lawyer preparing a class action lawsuit against the hospital says he now has 23 plaintiffs. And the state plans to start allowing possibly infected patients to get tested somewhere other than the hospital

Insuring Baby boomers testing positive for HCV

In May the CDC finally stepped up to the plate by recommending that all baby boomers be tested for HCV. Recently a few articles published in the media have suggested that baby boomers testing positive for HCV may find themselves unable to obtain health insurance. Here is an excerpt from an article written by  @ the Huffington post on the subject.

Boomers' Hepatitis C Test And Denied Insurance Concerns Unwarranted, Experts Say

The Huffington Post | By
Headlines were made last month when the CDC released a draft proposal urging all baby boomers to get tested for hepatitis C, the blood-borne liver disease. Now there's a debate as to whether or not a positive test result for the chronic disease will ruin boomer's chances at receiving insurance, due to the dreaded pre-existing conditions clause insurers often use to deny coverage, MSNBC reports. 
The CDC is also aware of these concerns, said Dr. John Ward, director for the Center's division of viral hepatitis, in a statement. "Considerations regarding insurance coverage are real," Ward said, "affecting individuals and their loved ones..." 
With boomers accounting for 2 million of the 3.2 million Americans with the liver disease (which, if untreated, can lead to liver cancer or cirrhosis), the anxiety is understandable; many infected individuals don't even know they have it, but they may be less willing to receive the test if it may lead to being denied for insurance. Yet these concerns are overblown, if not entirely a moot point, some experts say. 
"These types of diseases that couldn’t be treated before, people can now get insurance coverage," said Jon Allen, a risk manager at Trumark Financial, a Danville, CA insurance services firm, with knowledge of hepatitis C and insurance claims.  
At worst, Allen said, those suffering from really serious cases of the disease may see a higher rate ("maybe two times the standard rate"), but "they’re still insurable," he said. "We’ve had clients who have gone through treatment and [the virus] is virtual undecteable in their bodies. We’ve seen those people get standard-issue policies. 
"Most of these people are afraid to tell you anything because they think it’s hard to get insurance," said Allen. "It’s the other way around. The more you’re willing to share with companies [the better]."
Continue reading @ Huffington Post


A new site is up and running lending support to caregivers and hepatitis C patients undergoing triple therapy, click here to view the support website.

Hepatitis C support group sharing insights and battling stigmas
Tyler Clarke
In a community battling hepatitis C rates that more than double the provincial rate, Prince Albert’s Hepatitis C Support Group serves an important role.

“The clients that come to our support groups may be family members of people living with the virus and they might want to learn more,” registered nurse Shelley Crawford said.

“They might be clients living with the virus themselves and might want to learn more about the treatments.

Crawford heads the monthly Hepatitis C Support Group at the Prince Albert Sexual Health Clinic

The next Hepatitis C Support Group meeting will take place Wednesday, June 27, at the Prince Albert Sexual Health Clinic, located at 101 15th St. E.
Continue reading........

Healthy You

Licorice Root;
Licorice root should be used carefully because it can have significant side effects, including high blood pressure, salt and water retention, and potassium loss. It also can have potentially dangerous interactions with medications such as diuretics, certain heart medications, and corticosteroids.
Read more at WebMD

Licorice Root Extract Decreases Liver Enzyme Levels
Date: 05-31-2012 HC#051231-449

Hajiaghamohammadi AK, Ziaee A, Samimi R. The efficacy of licorice root extract in decreasing transaminase activities in non-alcoholic fatty liver disease: a randomized controlled clinical trial. Phytother Res. 2012; [epub ahead of print]. doi:10.1002/ptr.3728.

Non-alcoholic fatty liver disease (NAFLD) can lead to cirrhosis and possible liver transplantation. A common liver disorder, NAFLD affects 20-40% of the Western population1 (the Mayo Clinic Health Letter2 estimates that the disorder affects "up to 20% of American adults") and 5-35% of those in Pacific and Asian countries.3 Non-alcoholic steatohepatitis (NASH), is a type of progressive NAFLD, resulting in inflammation and liver scarring (fibrosis); such scars can harden the liver and impair its ability to function properly, a condition known as cirrhosis. Only about 5% of people with NAFLD develop cirrhosis, liver failure, or hepatocellular carcinoma. NASH is the third leading cause of cirrhosis in US adults, becoming a more common reason for liver transplants.2

Major risk factors for NAFLD are obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. Modification of risk factors is generally recommended for the disease. Licorice (Glycyrrhiza glabra) root has been used to treat stomach ulcers, bronchitis, and sore throat, as well as viral infections. Its major bioactive component, glycyrrhizin, possesses anti-inflammatory, antioxidant, and immune-modulating properties. Licorice has also been reported to reduce liver inflammation and hepatic injury; however, the mechanism for these properties is unclear. These authors conducted a randomized, double-blind clinical trial to investigate the effects of licorice on NAFLD.

The study was conducted at the Gastrointestinal and Liver Clinic of Qazvin in central Iran. The presence of NAFLD confirmed by sonography and the presence of elevated levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were the inclusion criteria. All subjects underwent a complete history of drug and alcohol consumption and were checked for autoimmune hepatitis and viral markers.

Sixty-six patients (38 men and 28 women) were enrolled and completed the study. They were divided randomly into 2 groups:

the treatment group (n=33), who received 1 capsule containing 2 g aqueous licorice root extract alone (20% glycyrrhizin) daily for 2 months (no other information is provided),
and the control group (n=33), who received 1 capsule containing 2 g starch daily for 2 months.

Weight, body mass index (BMI), and liver transaminase levels were measured for each subject before and after the study. The mean age of the treatment group was 40 years and the mean age of the control group was 40.5 years.

The authors report that for the treatment group, the mean BMI decreased from 30 kg/m2 at baseline to 29.20 kg/m2 after treatment (P>0.05). In the control group, mean BMI increased from 29.10 kg/m2 to 29.22 kg/m2 (P>0.05).

The mean serum ALT level decreased from 65.09 IU/mL at baseline to 51.27 IU/mL after treatment with licorice (P<0.001). In the control group, the ALT level decreased (though not significantly) from 66.90 IU/mL to 62.77 IU/mL (P>0.05). The mean serum AST level decreased in both groups during the study: a significant drop was seen in the treatment group, from 58.18 IU/mL to 49.45 IU/mL (P<0.001); and a nonsignificant decrease was reported in the control group, from 57.86 IU/mL to 54.81 IU/mL (P>0.05).

Although no data are available on NAFLD treatment with licorice root extract, some studies have shown that glycyrrhizin could improve lipoprotein lipase expression, insulin sensitivity, and serum lipid levels in rats.4, 5

According to the authors, the effect of licorice on liver histology (determined by liver biopsy) was not studied because of the invasiveness of the biopsy. Also, it is unclear whether the level of reduction in transaminases is clinically significant and whether transaminases are the best markers of NAFLD, say the authors.

Although the authors suggest that future studies could include more detailed tests of liver function and liver histology in addition to the measurement of liver enzymes, they conclude that licorice root extract appears safe and may be considered in the treatment of elevated liver enzymes in NAFLD.
—Shari Henson

Study: Omega-3 lowers inflammation in overweight older adults

June 20
COLUMBUS, Ohio - New research shows that omega-3 fatty acid supplements can lower inflammation in healthy, but overweight, middle-aged and older adults, suggesting that regular use of these supplements could help protect against and treat certain illnesses.

Four months of omega-3 supplementation decreased one protein in the blood that signals the presence of inflammation by an average of more than 10 percent, and led to a modest decrease in one other inflammation marker. In comparison, participants taking placebos as a group saw average increases of 36 percent and 12 percent, respectively, of those same markers.

Chronic inflammation is linked to numerous conditions, including coronary heart disease, Type 2 diabetes, arthritis and Alzheimer’s disease, as well as the frailty and functional decline that can accompany aging.

Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids in their supplements. Polyunsaturated fatty acids are considered“good fats” that, when consumed in proper quantities, are associated with a variety of health benefits. Study participants taking a placebo consumed pills containing less than 2 teaspoons per day of a mix of oils representing a typical American’s daily dietary oil intake. 

“Omega-3 fatty acids may be both protective so that inflammation doesn’t go up, as well as therapeutic by helping inflammation go down,” said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State University and lead author of the study.

“This is the first study to show that omega-3 supplementation leads to changes in inflammatory markers in the blood in overweight but otherwise healthy people. In terms of regulating inflammation when people are already healthy, this is an important study, in that it suggests one way to keep them healthy.”

The study is published online and scheduled for later print publication in the journal Brain, Behavior and Immunity.

The scientists recruited 138 adults - 45 men and 93 women - who were in good health, but who were either overweight or obese and lived sedentary lives. Their average age was 51 years. Based on body mass index, a measure of weight relative to height, 91 percent of the participants were overweight and 47 percent were obese.

Inflammation tends to accompany excess body fat, so the researchers recruited participants who were most likely high in pro-inflammatory blood compounds at the beginning of the study.

“We wanted to have enough room to see a downward trend. Most other trials testing the effects of omega-3 supplements on inflammation used people who were seriously diseased or skinny and healthy,” said Kiecolt-Glaser, also an investigator in Ohio State’s Institute for Behavioral Medicine Research (IBMR). “You can see results in people with serious diseases, but there’s a lot of other noise in that system. We wanted to make sure we were studying results in people who were fairly fit but who weren’t exercising, because exercise can clearly lower inflammation.”

The researchers also excluded from participation people taking a variety of medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

Participants received either a placebo or one of two different doses of omega-3 fatty acids - either 2.5 grams or 1.25 grams per day. The supplements were calibrated to contain a ratio of the two fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than does DHA.

After four months, participants who had taken the omega-3 supplements had significantly lower levels in their blood of two proteins that are markers of inflammation, also called pro-inflammatory cytokines. The low-dose group showed an average 10 percent decrease in the cytokine interleukin-6 (IL-6), and the high-dose group’s overall IL-6 dropped by 12 percent. In comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

Levels of the cytokine tumor necrosis factor-alpha (TNF-a) also dropped, but in a more modest way, by 0.2 percent and 2.3 percent in the low- and high-dose groups, respectively. The placebo group’s TNF-a increased by an average of 12 percent.

IL-6 and TNF-a are two of a family of six cytokines that, when stimulated, produce an inflammatory response to a stressor such as an injury or infection, said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the IBMR.

“You need this good inflammation for an initial response, but if it stays up, and inflammation becomes chronic, then you’ve got a problem,” Glaser said. “Our research and studies done by others have shown that these two cytokines are clearly related to overall health - and when they’re elevated in the blood, that is not good for overall health. So the more ways we can find to lower them, the better.”

Statistically, there was no significant difference in lowered inflammation between the two doses, but each dose clearly produced cytokine reductions that differed significantly from the placebo group.

“These data support the idea that a higher dose of omega-3 is not necessarily better than a lower dose in terms of prevention of inflammation,” said Martha Belury, professor of human nutrition at Ohio State and a co-author of the study.

“Omega-3 fatty acids may be both protective so that inflammation doesn’t go up, as well as therapeutic by helping inflammation go down.”

However, levels of omega-3 fatty acids in participants’ blood increased according to which dose they consumed, which improved their ratio of omega-6 fatty acids to omega-3 fatty acids. The current typical American diet contains between 15 and 17 times more omega-6 than omega-3, a ratio that researchers suggest should be lowered to 4-to-1, or even 2-to-1, to improve overall health.

“Scientists tend to agree that the best way to gauge a person’s omega-3 status is to see whether that ratio goes down,” Belury said. “That’s what we saw in this study, and it was achieved through supplementation. We wanted participants to maintain normal diets and simply add this modest amount of oil to their existing diet. We expected and we found that their blood plasma omega-3 fatty acids went up in a dose-responsive manner.”

The Food and Drug Administration considers daily omega-3 supplementation of up to 3 grams to be “generally regarded as safe.” The doses in this study were within those safety parameters, but the researchers did not extend their findings to make a general recommendation about omega-3 supplementation.

“Although omega-3 fatty acids cannot take the place of good health behaviors, people with established inflammatory diseases or conditions may benefit from their use,” Kiecolt-Glaser said.

The researchers also sought to determine whether omega-3 fatty acids could reduce depression symptoms, but participants had relatively few symptoms to begin with so no significant reductions were seen. Depression is also associated with chronic inflammation, but research hasn’t yet fully defined the mechanisms behind that relationship.

This work was supported in part by grants from the National Institutes of Health. OmegaBrite, a company based in Waltham, Mass., supplied the supplements as an unrestricted gift but did not participate in the study design, results or publication.

Additional co-authors, all at Ohio State, include Rebecca Andridge of the Division of Biostatistics; William Malarkey of the IBMR and the departments of Psychiatry and Internal Medicine; and Beom Seuk Hwang of the IBMR and biostatistics.

No Impact on Lipids With Vitamin-D Supplementation
Although vitamin D has been tied to cardiovascular disease prevention, this new study fails to confirm the results observed in cross-sectional studies and casts some doubt on the benefits of vitamin-D supplementation...Continue reading..


—Updated Book Evaluates Most Relevant Science For Assessing the Benefits of Specific Supplements--

The Benefits of Nutritional Supplements can be viewed and/or downloaded, chapter by chapter, or in its entirety, at no charge at CRN’s website.

WASHINGTON, D.C., June 20, 2012—The Council for Responsible Nutrition (CRN), the dietary supplement industry’s leading trade association, today released its comprehensive report, The Benefits of Nutritional Supplements (4th Edition). The updated book, which assesses the current state of the science on the health benefits associated with select nutritional supplements, finds consistent and adequate use of these products contributes to overall health and wellness throughout all age groups, lifestyles, and life stages.

Specifically, the report addresses the current state of the science regarding multivitamins and other supplements, including antioxidants (vitamins C and E), calcium, long chain omega-3 fatty acids (fish oils), vitamin D, vitamins B-6 and B-12, fiber and folic acid. It includes studies that demonstrate benefit as well as studies with null results and also addresses studies that purport to have found harm. It discusses who needs dietary supplements (nearly everyone), who takes dietary supplements (most everyone), and who recommends dietary supplements—the majority of many physician specialists (primary care physicians, OB/GYNs, cardiologists, dermatologists, and orthopedists), as well as other health professionals (nurses, nurse practitioners, pharmacists, and registered dietitians).

“In updating the fourth edition of the report, we highlighted current research demonstrating the health benefits provided by consistent use of many of these nutrients. We assessed not only the studies with favorable outcomes, but also those studies with ‘null’ or ‘negative’ findings, to paint a thorough picture of the state of the science surrounding these nutrients,” said the report’s author, Annette Dickinson, Ph.D., past president and current consultant for CRN. “And because we evaluate relevant scientific studies throughout the report, it was essential for us also to delve into the current debate over nutrient benefits—what is working, what could be improved, and what many experts in the field suggest.”

The updated report also reviews issues surrounding supplements and mortality, as well as the importance of select nutrients during key life stages, including during pregnancy and throughout the aging process. It reminds readers that even the most conscientious consumers find it difficult to get all the nutrients they need from food alone—and taking supplements is an effective and affordable way to fill a number of known nutrient gaps and help maintain overall good health.

“What is so important about this book is that instead of looking at individual studies, one at a time, and asking consumers to make decisions based on what often is a flip-flop of results, this book tracks the research so that individual studies can be placed in an overall context, more effectively reflecting the overall state of the science,” said CRN President & CEO Steve Mister, who wrote the introduction to the book. “Science is complex and constantly evolving, at times in unpredictable ways. The book addresses that evolution.”

Dr. Dickinson, an expert on vitamins, minerals, and other supplements, has worked in the nutrition field for more than four decades. In 1995, President Clinton appointed Dr. Dickinson to the Commission on Dietary Supplement Labels, and in 2002 she was named to a three-year term on the Food Advisory Committee of the Food and Drug Administration (FDA). She began working for CRN in 1973, primarily responsible for scientific and regulatory affairs, then serving as CRN’s president from 2002-2005. She currently consults for CRN and other clients on nutrition issues, and is also an adjunct professor in the Department of Food Science and Nutrition at the University of Minnesota. Dr. Dickinson has authored numerous papers and frequently speaks on the topic of dietary supplements to policy-making, scientific and other audiences. The first edition of The Benefits of Nutritional Supplements was published in 1987.

Off The Cuff

New Bird-Flu Study Shows Virus's Pandemic Potential
In a new experiment showing how the virus that causes bird flu might spark a human pandemic, scientists induced five genetic changes in the bug, transforming it into a type capable of airborne transmission between mammals. 
The findings signal how the virus, which has killed nearly 60% of about 600 people known to have been infected in more than a dozen countries since 2003, could pose a much greater public-health risk in the future. Two of the mutations the scientists created already circulate in birds and people, and natural evolution could bring about the remaining three, researchers said.
The findings appear in the journal Science, which on Thursday published several papers and commentaries about the virus—also known as H5N1. The studies were funded by the U.S. National Institutes of Health and other groups.
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