Scientists discover protein that boosts immunity to viruses and cance

Scientists have discovered a protein that plays a central role in promoting immunity to viruses and cancer, opening the door to new therapies.

Experiments in mice and human cells have shown that the protein promotes the proliferation of cytotoxic T cells, which kill cancer cells and cells infected with viruses. The discovery was unexpected because the new protein had no known function and doesn’t resemble any other protein.

Researchers from Imperial College London who led the study are now developing a gene therapy designed to boost the infection-fighting cells, and hope to begin human trials in three years.

The study also involved researchers at Queen Mary University of London, ETH Zurich and Harvard Medical School. Their discovery, which has been six years in the making, is reported today in the journal Science.

Cytotoxic T cells are an important component of the immune system, but when faced with serious infections or advanced cancer, they are often unable to proliferate in large enough quantities to fight the disease.

By screening mice with genetic mutations, the Imperial team discovered a strain of mice that produced 10 times as many cytotoxic T cells when infected with a virus compared with normal mice. These mice suppressed the infection more effectively, and were more resistant to cancer. They also produced more of a second type of T cells, memory cells, enabling them to recognise infections they have encountered previously and launch a rapid response.

The mice with enhanced immunity produced high levels of a hitherto unknown protein, which the researchers named lymphocyte expansion molecule, or LEM. They went on to show that LEM modulates the proliferation of human T cells as well as in mice.

The researchers now aim to develop a gene therapy designed to improve immunity by boosting the production of LEM. With the support of Imperial Innovations, the technology commercialisation company for the College, the researchers have filed two patents. A company called ImmunarT has been formed with the aim of commercialising the technology.

Professor Philip Ashton-Rickardt from the Section of Immunobiology in the Department of Medicine at Imperial, who led the study, said: “Cancer cells have ways to suppress T cell activity, helping them to escape the immune system. Genetically engineering T cells to augment their ability to fight cancer has been a goal for some time and techniques for modifying them already exist. By introducing an active version of the LEM gene into the T cells of cancer patients, we hope we can provide a robust treatment for patients.

“Next we will test the therapy in mice, make sure it is safe and see if it can be combined with other therapies. If all goes well, we hope to be ready to carry out human trials in about three years.”

Dr Claudio Mauro, who led the research from the Centre for Biochemical Pharmacology, based within Queen Mary University of London’s William Harvey Research Institute, said: “This study has identified the novel protein LEM and unlocked an unexpected way of enhancing the ability of our immune system to fight viruses or cancers. This is based on the ability of the protein LEM to regulate specific energy circuits, and particularly mitochondrial respiration, in a subset of white blood cells known as cytotoxic T cells. This discovery has immediate consequences for the delivery of innovative therapeutic approaches to cancer. Its ramifications, however, are far greater as they can help explaining the biological mechanisms of widespread human diseases involving altered immune and inflammatory responses. These include chronic inflammatory and autoimmune disorders, such as atherosclerosis and rheumatoid arthritis.”

The research was funded by the Medical Research Council, the Wellcome Trust and the British Heart Foundation.

Dr Mike Turner, Head of Infection and Immunobiology at The Wellcome Trust, said: “The discovery of a protein that could boost the immune response to not only cancer, but also to viruses, is a fascinating one. Further investigation in animal models is needed before human trials can commence, but there is potential for a new type of treatment that capitalises on the immune system’s innate ability to detect and kill abnormal cells.”

Story Source:

The above story is based on materials provided by Imperial College London. The original article was written by Sam Wong. Note: Materials may be edited for content and length.

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Important connection between the mouth and heart

A new study from the Forsyth Institute is helping to shed more light on the important connection between the mouth and heart. According to research recently published online by the American Heart Association, scientists at Forsyth and Boston University have demonstrated that using an oral topical remedy to reduce inflammation associated with periodontitis, more commonly known as gum disease, also results in the prevention of vascular inflammation and can lower the risk of heart attack.

This study is the first time researchers anywhere have demonstrated the ability of an oral treatment for gum disease to also reduce inflammation in the artery wall. The active ingredient is an inflammation resolving molecule, known as Resolvin E1. This discovery further underscores the increasing body of evidence showcasing how problems in the mouth -- and how they are treated -- can have life changing influences on other key systems in the body, such as the heart in this case.

"Our research is helping to underscore the very real link between oral health and heart disease," said Lead Investigator Hatice Hasturk, DDS, PhD, an associate member of Forsyth's Department of Applied Oral Sciences and director of Forsyth's Center for Clinical and Translational Research. "The general public understands the connection between heart health and overall wellness, and often takes appropriate steps to prevent heart disease. More education is needed to elevate oral wellness into the same category in light of proven connections to major health conditions."

According to the CDC, heart disease accounts for one in four deaths in the United States, and the rate continues to rise. Forsyth's findings suggest a need to expand the public's understanding of risk factors beyond cholesterol, smoking, hypertension and diabetes to include a focus on oral health. With support from the scientific community, Forsyth aims to generate greater awareness of gum disease (affecting 64.7 million American adults according to the CDC) as a critical risk factor for heart disease, independent from diet and lifestyle.

The study, titled, "Resolvin E1 Prevents Atheromatous Plaque Formation," will be published in print in the May issue of Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a journal of the American Heart Association. It is the first paper to show a rabbit model of accelerated heart disease, demonstrating a range of atherosclerotic plaque stages that more closely resemble those in humans without genetic modification of the animal. This research is authored by Hatice Hasturk, Rima Abdallah, Alpdogan Kantarci, Daniel Nguyen, Nicholas Giordano, James Hamilton and Thomas E. Van Dyke.

Story Source:

The above story is based on materials provided by Forsyth Institute. Note: Materials may be edited for content and length.


Journal Reference:
Hatice Hasturk, Rima Abdallah, Alpdogan Kantarci, Daniel Nguyen, Nicholas Giordano, James Hamilton and Thomas E. Van Dyke. Resolvin E1 Prevents Atheromatous Plaque Formation. Arteriosclerosis, Thrombosis, and Vascular Biology, May 2015

Vitamin D research history, and toxicity examples.

I include this entire article, to make a point that massive is about 1,000 time what I believe is beneficial  (a planned and monitored 50,000 iu per day dose of D3.) Here is the history of Vitamin D3 use and research. 

____________________________

The article:

  

Warning: If you intend to take massive doses of vitamin D based on this newsletter, which I highly recommend you do not, read the entire newsletter. In addition, accurate determination of side effects of massive doses of vitamin D was not available in the early 1930s, nor was accurate determination of the true amount in each pill possible.

Is 2,000,000 IU/day of vitamin D toxic?

Ask Gary Null, alternative medicine guru and entrepreneur. He took his own supplement, Ultimate Power Meal, for a month and became extremely ill; one batch of Power Meal apparently contained 1,000 times more vitamin D than it should. That is, it contained 2,000,000 IU of vitamin D3 per serving instead of 2,000 IU per serving. Mr. Null became sicker and sicker as he gulped it down.

1. LA Times: Supplements guru sues over his own product
2. New York Post: Putting the ‘die’ in diet

After suing his own supplier for permanent physical damage, Mr. Null then reported it took 3 months to get the extra vitamin D out of his system and that he is now alive and well.

New York Post: ‘Death’ is now Null and void

If Mr. Null took it for the full month that he claims, and if his Power Meal contained 2,000,000 IU per dose, Mr. Null consumed 60,000,000 IU in one month. Could he really be fine now with no lasting injuries?

In an attempt to answer that question, I went back to the 1930s and 40s.

Massive doses in the 1930s

The earliest references I could find to enormous doses of vitamin D were in the 1930s. In 1935, Drs. Dreyer and Reed, of the University of Illinois School of Medicine, published their observations on 700 patients treated with “massive” doses of vitamin D for up to two years.1

First, the authors report that vitamin D had remarkable treatment effects on all kinds of arthritis, especially rheumatoid arthritis. They report on 67 arthritic patients so treated, with 75% of the patients responding most dramatically.

The dose used? Drs. Dreyer and Reed started all patients on 200,000 IU per day! They started some patients on 200,000 IU/day of D2 and others on 200,000 IU/day of D3, noticing no difference in efficacy. They used vitamin D preparations made by Mead Johnson, Glaxo, and Abbott.

“If there was no improvement and no evidence of sensitivity, the daily dose was increased by 50,000 units each week until there was some improvement or evidence of overdosage. In some stubborn cases, it was found necessary to increase to 600,000 or even 1,000,000 units for a few days and then reduce to 200,000 to 500,000 units. Most of our results have been obtained with daily doses of 300,000 to 500,000 units.”

The authors report that 63 of the 700 patients on this dosage became clinically toxic. That is, about 10% of the patients on these doses became sick (toxic) from the vitamin D. Today, we usually think of vitamin D toxicity as asymptomatic high blood calcium but these were old time doctors; toxic meant sick.

How did they treat the 63 patients who became sick from massive doses of vitamin D? Hospitalize them in the ICU? No, they simply stopped the vitamin D, told them to drink plenty of fluids, waited for the symptoms of toxicity to dissipate, and then restarted them on a lower dose, such as 150,000 IU per day.

The authors do mention that many of the patients had high blood calcium, one in the 20s, but if the patients were not sick, the doctors didn’t care about the calcium. As the authors did not draw serum calcium on all of the 700 patients, we don’t know what percentage of patients on these doses became hypercalcemic.

Symptoms of Toxicity

The authors report that the symptoms of vitamin D toxicity began with persistent nausea, which the doctors instructed their patients to be on the lookout for, as well as increased frequency of urination without increased volume of urine. Weakness and increased thirst were common, and “if the treatment is continued, diarrhea, gripping pain in the gastrointestinal tract, and vomiting.” The authors bragged that they could not report on pathological findings in toxicity, because none of their 700 patients had died and “come to autopsy.”

In 1934, the Journal of the American Medical Association published a study on vitamin D overdose:Reed CI. Symptoms of Viosterol overdosage in human subjects. JAMA. 1934;102:1745–1748.

They reported on 300 patients given high doses of vitamin D2 for asthma and hay fever. The author reported that each cc contained 900,000 IU of vitamin D2. The good doctor gave one patient 3 cc per day for five days (that would be a total dose of 13.5 million units) “without the slightest evidence of injury.”

However, in his conclusion, Dr. Reed was much more conservative:

“There need be little apprehension about the administration of amounts ranging up to 150,000 international units daily for indefinite periods. Larger amounts had better be limited to periods of a few months at most, depending on the therapeutic effects desired.”

Dr. Rappaport and colleagues at the University of Illinois studied the effects of Viosterol (vitamin D2) on asthma and hay fever in 212 patients, giving placebo to a control group. The authors reported that 82% of the hay fever patients and 96% of the asthma patients “experienced definitive significant relief.” The authors concluded that the “optimum dose” of vitamin D was 60,000 to 300,000 IU per day.

Rappaprt BZ, et al. The treatment of hay fever and asthma with Viosterol of high potency. J. of Allergy. 1934;5:541–553.

Why these doctors did not try 5,000 or 10,000 IU/day, instead of 200,000 IU/day, I could not ascertain.

Death in the 1940s

Things began to change in the 1940s. In 1946, two case reports of fatal vitamin D toxicity in adults (the authors report five previous fatal cases in children) appeared in the medical literature.1

Another case report of a fatal dose of vitamin D in adults appeared in 1947. This death was from Ertron, vitamin D2, at a dose of 150,000 IU daily for 18 months, and it included a description of foot lesions similar to what Gary Null reported. This paper is free to download and I suggest everyone who is flirting with the idea of using massive doses of vitamin D obtain it and read it. It is chilling to read the detailed autopsy report.2

By 1948, the medical community began condemning the use of such massive doses of vitamin D as evidenced by a paper from Johns Hopkins University:

Howard JE and Meyer RJ. Intoxication with vitamin D. J. Clin. Endocrinology. 1948;8(11);895–910.

The authors reference 12 earlier papers on vitamin D intoxication with calcification of everything from the kidneys to the sclera of the eyes. The first symptoms of vitamin D toxicity in their series of 11 patients were weight loss and fatigue, which occurred before the anorexia (poor appetite) and vomiting. All of their patients suffered from kidney damage and anemia. Virtually all of the patients had a characteristic eye lesion, which are calcium deposits in the sclera and cornea, just beneath the conjunctival basement membrane.

All patients had high blood calcium, ranging from 12.4 to 15.1 mg per 100 cc. Dosages of vitamin D ranged from the lowest at 150,000 IU/day for 4 months (serum calcium 13.9) to the highest at 500,000 IU/day for 18 months (serum calcium 14.3). They reported on another patient who developed hypercalcemia after she reported taking 300,000 IU of vitamin D2 for only 2 weeks; she also had eye lesions evident on slit lamp exam. Although accurate follow up was not possible due to the fact the patients came from around the country, no patients died but some suffered permanent renal damage from the excessive doses of vitamin D.

The treatment the authors used for vitamin D toxicity was discontinuing the vitamin D, drinking 4,000 cc of fluid per day, and a low calcium diet. Improvement occurred within 2–8 weeks when nausea, vomiting, and lassitude disappeared. Blood calcium fell in all patients by one month but continued to be elevated for as long as a year in one patient.

These reports of toxicity were all the medical profession needed to condemn vitamin D as dangerous, as I learned in medical school in the early 1970s. The dark ages of vitamin D meant that for several generations of doctors, vitamin D was toxic at all but the most meaningless doses. Its use to treat asthma and arthritis became verboten. For fifty years, doctors forgot about vitamin D — other than vitamin D deficient rickets — because of fear of toxicity. During these dark ages, the Food and Nutrition Board periodically reviewed vitamin D and repeatedly distributed toxicity alarms, along with their recommendations that we only take insignificant doses.

Out of the dark ages

Then, at the turn of the century, Professor Reinhold Vieth of the University of Toronto showed us the way out of the dark ages with an objective review of the toxicity literature.

What Vieth’s paper showed was that there is a difference between 5,000 IU per day and 50,000 IU per day, the first being a physiological dose and the second being a pharmacological dose, a drug. However, in 1999 the world was using neither dose properly, in that no doctors were prescribing 5,000 IU per day and no scientists were studying 50,000 IU per day.

After Vieth’s paper, in the first few years of this century, a steady stream of vitamin D papers began flowing out of research labs, with the number of publications increasing every year. For example, scientists published 1,582 new papers on vitamin D in the first six months of 2010. Very few are about toxicity, instead they cover a breathtaking variety of diseases. These papers raise the possibility that many of the diseases that we take as being part of the human condition are not part of the human condition, instead they are simply the result of the toxicity scare: vitamin D deficiency. That is, these diseases are simply different presentations of the same deficiency. In that way, vitamin D deficiency is similar to syphilis.

Sir William Osler said, “Know syphilis in all its manifestations and relations and all other things clinical will be added unto you. Know syphilis and the whole of medicine is opened to you.” He called it the “Great Imitator,” because late stages of syphilis simulate almost every disease known to man. Smoking is similar, some smokers get emphysema, some lung cancer, some heart disease, some bladder cancer, some pancreatic cancer, and some live to be 100. Increasingly, vitamin D deficiency looks as if it may do the same thing. Some vitamin D deficient people will get asthma, others cancer, others heart disease, others autoimmune illness, and some will live to be 100.

Let’s look at one rare disease, childhood multiple sclerosis, a nightmare for any parent to face. The child will have problems with vision, co-ordination, or balance, with relapses and remissions, that is the disease seems to come and go. Recently, Dr. Ellen Mowry and her colleagues discovered that these relapses, these periods of active autoimmune illness, are associated with low levels of vitamin D. The disease comes and goes as vitamin D levels come and go. Dr. Mowrey speculated that a 15 ng/mL increase in vitamin D levels would cut the relapse rate in half.3

Dr. Mowry did not raise the fundamental question: would these children have become ill in the first place if they had adequate amounts of vitamin D during their growth and development? The average vitamin D level of these 110 children was 22 ng/mL, so Dr. Morey could not say what an increase to 50 ng/mL would do, nor could she say if low vitamin D levels were what allowed the disease to appear in the first place.

That is, is juvenile multiple sclerosis simply one of many possible presentations of childhood vitamin D deficiency? Some vitamin D deficient children will get multiple sclerosis, some asthma, some diabetes, some rickets, and others autism. That is, is vitamin D deficiency the modern day syphilis?

Unlike syphilis, vitamin D deficiency is largely an iatrogenic disease, caused by the medical profession’s near hysterical fear of vitamin D toxicity. Physicians simply forgot what Paracelsus said many years ago, “All things are poison and nothing is without poison, the dose alone permits something to be poisonous.” We went from intemperance in the 1930s to hysteria in the 1950s and we are only now coming to our senses.

We look around at the diseases debilitating our children, the triple A epidemics of autoimmune disorders, asthma, and autism. All are truly epidemic, all are debilitating or worse, and vitamin D is involved in all three. We failed to make sure our children had enough vitamin D throughout their growth and development and now our children suffer, in large part because of the hysteria over vitamin D toxicity.

What dose is toxic? I don’t know but I’d guess for some adults it is around 50,000 IU/day. However, it will vary widely and some people may get asymptomatic side effects on lower doses, such as kidney damage, without getting clinical signs of toxicity. Just because you feel fine, that does not mean your kidneys are fine.

Getting back to Mr. Gary Null and his ingestion of 60,000,000 IU over one month, could he have survived that dose? Apparently, the answer is yes, although I doubt he took it every day, especially as he got sicker and sicker. Could he have survived that dose without permanent kidney damage? I doubt it.

1

About John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.

View all posts by John Cannell, MD →

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Some specific cases of D3 toxicity. (They are hard to find)

More recent cases of Vitamin D overdose: from: > look here <

Several cases of vitamin D toxicity have just recently been reported in the literature, demonstrating the sort of very large daily amounts that may lead to ill health. All were due to some sort of error.

In the first case, a pharmacist’s dispensing error occurred when a physician prescribed 1,000 IU/day of D3. Since it was not a prescription item, the pharmacist assumed the doctor meant Rx Drisdol, which is 50,000 IU D2. So the patient, a 70-year old woman with mild dementia, began taking 50,000 IU/day of D2. She was also taking, for unknown reasons, 3,100 mg of calcium per day [Jacobsen et al. 2011].

After 3 months of this regimen, the woman developed signs of hypercalcemia: confusion, slurred speech, unstable gait, and increased fatigue. She was hospitalized for hypercalcemia and acute kidney injury secondary to hypervitaminosis D; her 25(OH)D level was 194 ng/mL. All vitamin D supplementation was discontinued and 5 months after discharge, the patient's serum calcium and vitamin D concentrations, as well as renal function, had returned to baseline values.

The second case involved an otherwise healthy man who developed fatigue, excessive thirst, frequent urination, and confusion after taking a commercial vitamin D supplement for 2 months. Three weeks after becoming symptomatic he was admitted to the hospital in a coma with a vitamin D level of 1,220 ng/mL, calcium of 15, elevated urine calcium/creatinine ratio, and mild anemia. He had been taking a supplement (“Formula F”) labeled to contain 1,600 IU of vitamin D but which actually contained 186,400 IU per capsule due to manufacturing error. Additionally, the product label recommended 10 capsules per day, so the patient had been taking 1,864,000 IU daily for two months. After treatment, calcium returned to normal in 3 weeks; the vitamin D level and the creatinine returned to normal in a year [Araki et al. 2011].

In the third case, reported in the Araki et al. paper above, a 40-year-old man developed excessive thirst, frequent urination, muscle aches, nausea, vomiting, elevated calcium, elevated creatinine and Ca/Cr ratio, mild anemia, and a 25(OH)D level of 645 ng/mL. He reported taking a supplement for a month (“ Gary Null’s Ultimate Power Meal”), which mistakenly contained 970,000 IU of vitamin D per serving. Following treatment, calcium returned to normal in several days, kidney function returned to normal in 4 weeks, and vitamin D level normalized in 10 months.

It is noteworthy that in these cases — involving extremely large amounts of vitamin D taken for an extended time — there were no deaths or permanent injuries, once proper treatment was provided. While the human body appears to have greater tolerance for excessive vitamin D supplementation than many believe, it is still advised that caution be exercised when prescribing any vitamin D supplement or in selecting a good quality over-the-counter product. Additionally, some have recommended that persons taking more than 10,000 IU/day of vitamin D should have their 25(OH)D levels checked regularly, and that the level should be maintained below 100 ng/mL [Vitamin D Council here].
REFERENCE:
> Araki T, Holick MF, Alfonso BD, et al. Vitamin D Intoxication with Severe Hypercalcemia due to Manufacturing and Labeling Errors of Two Dietary Supplements Made in the United States. J Clin Endocrinol Metab. 2011(Sep 14); online ahead of print [abstract here].
> Jacobsen RB, Hronek BW, Schmidt GA, Schilling ML Hypervitaminosis D Associated with a Vitamin D Dispensing Error (October). Ann Pharmacother. 2011(Sep 13); online ahead of print [ abstract here].
> Skversky AL, Kumar J, Abramowitz MK, et al. Association of Glucocorticoid Use and Low 25-Hydroxyvitamin D Levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001–2006. JCEM. 2011(Sep 28); online ahead of print [ abstract here].


Acknowledgment: Thanks to John Cannell, MD, of the Vitamin D Council, for providing some of the details regarding the above case examples.

Cheap Allergy Drug May Hold Potential as Hepatitis C Treatment

WEDNESDAY, April 8, 2015 (HealthDay News) -- Preliminary lab research suggests a hay fever drug that costs about 50 cents a pill has the potential to treat hepatitis C, a stubborn disease that has spawned drugs that sell for $1,000 a dose.

It's too early to know if the antihistamine chlorcyclizine HCI will work in people as a treatment for hepatitis C. Still, the new research suggests that "the drug blocks the virus getting into cells and is different from the current hepatitis C drugs, which block viral replication," said study co-author Dr. T. Jake Liang, a senior investigator with the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Moreover, "this drug complements the existing hepatitis C drugs and can be used in combination with them," Liang added.

Hepatitis C often leads to serious liver complications such as cirrhosis. Some expensive new medications are "astonishingly effective" with cure rates of more than 90 percent, said Dr. Douglas Dieterich, a professor of liver diseases at Icahn School of Medicine at Mount Sinai in New York City.

But the pills are more than $1,000 each and need to be taken for weeks, potentially costing $84,000 to $93,000, a recent analysis found. While more drugs are in the pipeline, Dieterich said they're likely to be just as pricey.

About 3.2 million Americans have hepatitis C, according to the U.S. Centers for Disease Control and Prevention. One recent study put the cost of getting the new drugs to patients at $65 billion over just five years.

For now, "only those with more advanced liver disease are obtaining access, due to high drug costs and restrictive policies of many public and private insurance carriers," said Dr. Joseph Lim, director of the viral hepatitis program at Yale University School of Medicine in New Haven, Conn.

Liang and his team have tried to determine if new uses of existing drugs might work to treat the disease. In this study, they grafted human liver cells into mice to test the allergy drug.

An over-the-counter antihistamine, chlorcyclizine HCl costs $16.98 for 30 pills when sold under the brand name Ahist.

Chlorcyclizine has been around for decades but is not widely used. But the researchers found that the drug appears to prevent an early stage of infection with hepatitis C.

The drug could be used in all kinds of hepatitis C patients, Liang said, and could help prevent re-infection in patients who undergo liver transplantation.

The research is early, and a number of challenges remain, however. For one thing, "we would have to use the currently accepted dosing for any clinical trial, because the drug at high doses may have significant side effects, such as drowsiness," Liang said. "It is possible that the current dosing may not be active against hepatitis C in people."

In addition, he said, scientists might have to modify the drug to minimize its antihistamine effect. "This effort will require additional pharmacological research and development," Liang said. Drowsiness and dry mouth are common side effects of older hay fever drugs.

Dieterich praised the study and said it offers hope that "there may be very cheap and available drugs" to treat hepatitis C.

But Lim said other drugs in development could succeed in driving down prices once they're released, raising the question about whether a medication like this one will be needed.

What's next? "Currently, we are trying to optimize this class of drugs in the laboratory and hopefully [test it] in people in the near future," Liang said.

The study appears in the April 8 issue of Science Translational Medicine.

More information

For more about hepatitis C, see the U.S. Centers for Disease Control and Prevention.





SOURCES: T. Jake Liang, M.D., senior investigator, Liver Diseases Branch, U.S. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.; Joseph Lim, M.D., associate professor, medicine, and director, Yale Viral Hepatitis Program, Yale University School of Medicine, New Haven, Conn.; Douglas Dieterich, M.D., professor, liver diseases, Icahn School of Medicine at Mount Sinai, New York City; April 8, 2015, Science Translational Medicine

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