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A Tiny Lab Finds Danger on Drugstore Shelves While the FDA Lags Behind

Anna Edney, Bloomberg News, November 9, 2022


David Light can’t wait to show off his tchotchkes. The curly haired scientist lights up with boyish enthusiasm when he picks up a black coffee mug from the endless array of memorabilia in his office. It’s emblazoned with the trademark lettering of Zantac, the blockbuster heartburn drug. He quickly moves on to a Zantac wine glass from 1983, when the heartburn drug was approved for sale in the US, and then a white and blue Zantac Swiss army knife. A globe, then a t-shirt, next a hat — all stamped with the drug’s branding.

One floor above his office is the lab where groundbreaking Zantac research took place. But Light didn’t create Zantac — he nearly destroyed it. In the process, he’s also become a stand-in, protecting the American public from cancer-causing chemicals in place of a federal regulator that’s failed to do the job.

Light is the co-founder and chief executive officer of Valisure, the independent testing lab that first released research showing that Zantac and its generic forms were contaminated with a toxic chemical known to cause cancer. The findings, published in 2019, helped lead to massive recalls and eventual market withdrawal. Some two dozen companies were selling versions of the drug at the time.

Valisure truly shot into the public eye last year when it was the first to warn that some widely used hand sanitizers had high levels of carcinogens. Next came the lab’s evidence of leukemia-causing benzene in sunscreens. Then Valisure alerted consumers to dangerous chemicals in spray antiperspirants, and, more recently, dry shampoos. The lab has also warned of contaminants in a popular diabetes treatment. Procter & Gamble Co., Johnson & Johnson, Unilever Plc, CVS Health Corp. and Beiersdorf AG have all issued recalls or halted sales following Valisure’s findings.

In the course of just three years, Valisure’s quest to hunt down cancer-causing chemicals in everyday products has impacted pharmaceuticals and consumer goods in markets worth an estimated $9 billion that touch the lives of tens of millions of Americans.

“I feel that we’ve already saved many lives,” Light said. “When such big numbers of people are exposed, years of exposure with a well-defined carcinogen, there is no doubt there’s unacceptable risk.”

On every step of that journey, the Food and Drug Administration, the agency responsible for safeguarding consumers from these problems, has lagged behind the small lab.

[….]

 Impurity Testing

The testing done by Valisure is routine and can be run by any company that makes pharmaceuticals. On a recent visit, a scientist in a white lab coat replicated the experiment on an older version of Zantac at Valisure’s lab in Connecticut. A vial of milky pink liquid disappears into a machine that costs more than some luxury cars. The liquid is vaporized and separated into its various components. After several minutes, there’s a readout on a nearby computer screen: There’s a tall peak, like an irregular rhythm on a heartrate monitor. The figure indicates high impurity levels.

Valisure first released its Zantac findings to the public in September 2019. It took roughly seven months for the FDA to finally force the drugmakers to pull Zantac products off the market.

GSK Plc, the creator and original seller of Zantac, maintains that there is “no consistent or reliable evidence” the drug “increases the risk for any type of cancer,” the company said in an emailed statement.  Sanofi, the most recent seller of the non-prescription version of the drug, said it “stands by the safety of the medicine today.”

Powerful Regulator

As problems with carcinogen-laden medications and consumer products continue to fall through the cracks, the FDA maintains it is up to companies to ensure their products are safe. The situation highlights one of the biggest challenges at the agency: It doesn’t conduct much testing for these types of contaminants.

“FDA doesn’t do routine testing,” said Scott Knoer, who served as the CEO of the American Pharmacists Association for two years before stepping down in June.

“I had always believed anything in the US was safe,” Knoer said. “It was not as thorough as I guess previous perception was.”

The FDA takes a risk-based approach to quality testing, said Harrison, the agency spokeswoman. Each year it focuses on analyzing a few dozen products with already known issues. For example, the agency tested many hand sanitizers in the year that ended Sept. 30, 2021.

Pharmaceutical Fees

The FDA has an enormous purview, overseeing not just food and drugs, but also medical devices, tobacco and cosmetics. Despite that, its budget is just half that of the Environmental Protection Agency or the Internal Revenue Service. And about two-thirds of the funding the FDA receives for its drug activities comes from user fees paid by pharmaceutical companies. Since the early 1990s, the FDA and drugmakers have negotiated a deal every five years that Congress then approves. That agreement between the FDA and drugmakers dictates what the FDA can then do with those user fees.

It costs a drug company more than $3 million in fees to submit a new drug application to the FDA for review. In exchange, the agency has to meet review deadlines to help speed up the application process. This all means the regulator has far fewer funds to put toward making sure drugs already on the market are safe. It also means the industry gets a lot of deference.

“User fees provide access to FDA decision-makers in ways that foster a cozier relationship between FDA and industry,” said Diana Zuckerman, president of the National Center for Health Research, a think tank that focuses on the safety of medical and consumer products.

The agency has taken heat in the last year and a half for approving an Alzheimer’s disease drug that wasn’t fully proven to work, leading to accusations that the body is too beholden to the drug industry. The FDA also let clear signs of problems at an Abbott Laboratories’ infant formula plant slip by for almost five months before overseeing a recall and temporary closure of the factory in February, which ultimately led to a national formula crisis. These fiascoes have consumed the agency at a time when it’s been overwhelmed by the race to approve Covid-19 treatments and vaccines. All the while, recalls of sunscreen, antiperspirants, hand sanitizers and dry shampoo keep piling up.

[….]

Carcinogens and Where They’re Found

Rather than embrace Valisure as a partner in protecting the public, the FDA instead turned combative.

On May 24, 2021, Valisure released its findings showing cancer-causing chemicals in sunscreens. Two days later, two FDA inspectors showed up at the lab, according to agency documents. They brought an FDA lawyer with them for three of the 11 days they were at Valisure. The three FDA employees were deployed to the Valisure lab at a time when the regulator was focused on conducting its most critical inspections amid a pandemic backlog.

Valisure has about 20 employees who work in an office space of about 6,000 square feet in New Haven, Connecticut. The FDA, to compare, operates in 3.1 million square feet of office and lab space on a sprawling campus in Silver Spring, Maryland. It has 18,000 employees and a $6 billion annual budget.

To read entire article, click here.

Testimony of Dr. Diana Zuckerman About I-omburtamab FDA Advisory Committee Meeting

October 28, 2022


I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  

My expertise is based on post-doc training in epidemiology and public health, my previous policy positions at Congressional Committees with oversight over FDA, my previous position at the US Department of Health and Human Services, and as a faculty member and researcher at Harvard and Yale. 

This is a terrible disease and the personal stories are very important.  What is the evidence that this treatment actually works?

The sponsor has provided data from 2 studies:

  1. A single center, single arm trial (Study 03-133) included 94 pediatric patients ages 0.9 to 13 years with CNS/LM relapsed neuroblastoma who received intracerebroventricular infusions.  Three doses were used: 25 mCi, 33.5 mCi, or 50 mCi, based on age. The Primary Endpoint was overall survival and the results showed 45% alive at 3 year.
  2. The second study is not completed yet.  The Interim report of this multi-center single arm study (Study 101) shows 20 patients with imaging evidence of CNS/LM disease.  The Sponsor reports 7 responders, but 3 of these are not confirmed.  That matters because transient responses are not necessarily meaningful, and therefore can’t be considered evidence.  The Primary Endpoint is 3-year overall survival, but those data are not yet available.

Safety

It is important to note that 19% of patients permanently discontinued using the drug due to an adverse reaction in Study 03-133 and 28% of patients in Study 101.  Most were due to myelosuppression.  However, 3% were due to chemical meningitis (3 cases in 03-133 and 1 case in Study 101), and there was one case of fatal intracranial hemorrhage

Shortcomings of the Studies

Only one study was completed and it wasn’t randomized or blinded or controlled.  The external control group was very small and they differed from the patients receiving the treatment, because the latter had more intensive prior treatment.  There were significant population differences as well as treatment differences between the treatment group and the external controls.  In addition, overall survival for this condition has improved since the control data sample was collected.

Therefore, we agree with FDA’s conclusion that differences in overall survival can’t be “reliably attributed” to the drug.  We also agree that “the application does not include reliable response rate data to provide supportive evidence.”

In Study 101, no patient demonstrated a response that can be unequivocally   attributed to the drug.  And there was no overall response rate calculated for Study 03-133  and only very limited overall response rate data in Study 101.

FDA has been the Gold Standard?  Do these data meet that standard?

The FDA Summary states: The comparator is too dissimilar to the treatment group.  There is no reliable information on tumor response rate.  Therefore, the submitted study cannot be considered an adequate and well-controlled trial necessary to establish effectiveness. That’s the standard that the law requires for FDA approval.

On the other hand, there is an unmet need. These children need treatment.  Should FDA be flexible even though the data are clearly inadequate?  Why isn’t this an accelerated approval application instead of a regular application? Are the data even good enough for accelerated approval?

Are FDA Decisions Perpetuating Poor Studies?

Why didn’t the sponsor conduct a randomized, double blind controlled trial?  This isn’t a rhetorical question.  What’s the incentive for any company to conduct a well-designed study if a poorly conducted study with questionable findings results in approval?  Those controversial decisions set a dangerous precedent.

Unfortunately, when FDA approves a drug based on inadequate data, all companies lose the incentive to conduct well-designed studies.  Not just the company whose product is approved, but all other companies as well.

Patients Deserve Better

We do patients and their families no favors by approving treatments that aren’t proven to work. 

FDA’s Expanded access program is the way to give patients access to experimental drugs, because it provides free treatments in a well monitored situation where the patients and families know that they are taking a risk using an experimental drug.  Why should patients pay to take an experimental drug, thinking it is proven safe because it is FDA approved?

I can’t believe I have to say this: Without an appropriate control group, it is not possible to provide evidence that patients and doctors need to make informed decisions.  Even a small study with a small well matched control group is better than nothing.

Unfortunately, the preponderance of evidence doesn’t support approval for this drug.

The Advisory Committee agreed with our assessment and voted 16-0 that the studies did not prove the drug improved overall survival. The FDA subsequently rejected the application.

NCHR Testimony at FDA Advisory Panel on Wound Dressings

October 26, 2022


I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. So I have no conflicts of interest. 

My expertise is based on post-doctoral training in epidemiology and public health, my previous policy positions at Congressional Committees with oversight over FDA, my previous position at the U.S. Department of Health and Human Services, and as a faculty member and researcher at Harvard and Yale. 

There are unique issues for the different types of wound dressings you are considering today, but they have some issues in common:

  1. They have been treated as 510k devices despite not being categorized as Class II or any other Class
  2. They have been used for years but FDA found very few studies pertaining to safety or effectiveness, and some were specific to particular types of surgery, such as diabetic foot ulcer care.  
  3. The information from FDA’s AEs reporting on the MDR system is  limited but the FDA has identified several potentially serious AEs, including toxicity, infections, and delays in wound healing.  These are important because they clearly can interfere with the success of surgery. 
  4. Most patients and surgeons assume that these products are proven safe and effective.  They would be surprised to know how little scientific evidence there is regarding safety and effectiveness.

You heard testimony from Madris Kinard from Device Events this morning, and saw her excellent analyses of adverse events based on information from the FDA database.  At our request, she also provided an analysis of wound dressings to our research center, based on the FDA total product life cycle database.  The results indicated thousands of reports of contamination and problems with non-sterile packaging of wound devices on the FDA.  Most were from the last 4 years. For the animal derived wound dressings, which are collagen dressings, there are 126 MDRs and 12 recalls.

FDA and other experts agree that MDRs are under-reported. It is a voluntary system, and as panel members mentioned this morning, it is difficult to distinguish between adverse events caused by the device vs. the procedure.  We all know that surgeons are very busy and do not strong incentives to report adverse events if the causes are unclear.  Keep in mind, for example, if a patient’s wound becomes infected, surgeons would not necessarily report it as an MDR for the wound dressing.

The FDA has delineated some very clear special controls for these devices if they are considered Class II and continue to be cleared through the 510k process.  These are good efforts that would improve upon the current regulatory policies for these devices.

But the special controls have 2 major shortcomings:

#1: They don’t include inspections, which could reduce harm caused by contamination and non-sterile packaging.

#2:  None of those controls will provide scientific data on the safety and effectiveness of any of these wound dressing products.   And that is the one crucial type of information that is missing. Insufficient information is currently available, especially regarding which specific products are safest and most effective for which indications.  The issue isn’t just different types of wound dressings, but the products made by different companies.  It is likely that some are better than others.  That is why I encourage you to urge the FDA to categorize wound dressings as Class III, so that we will finally have well designed clinical trials to determine safety and effectiveness. 

What about registries?  Registries can collect important information.  But as you consider all the medical devices being discussed today and tomorrow,  please remember that registries are controlled by medical societies and as such the data from them are not available to the public or the FDA, except for the information that those medical societies choose to make public.  So unfortunately, we can’t rely on registries to provide objective, comprehensive information about safety or effectiveness to the FDA or the public.

A Special Report: Can Breast Implants Cause Chronic Disease?

Julia Halpert, HealthCentral: October 25, 2022

With new FDA warnings, troubling research, and a growing online population sharing stories and symptoms, experts and women with implants weigh in.

JENNIFER JOHNSON, 43, of Wilcox, NE, underwent a preventative double-mastectomy—a surgical procedure that removes all tissue from both breasts—in July 2008 at age 29 after learning she carried the BRCA2 genetic mutation.

Research shows that having BRCA2 increases risk of developing breast cancer (BC) by 45%. Johnson’s family history didn’t make her keen to play the odds: Her mother died from the disease at 34, as did her sister Debbie at 39, while another sister, Valerie, was diagnosed with BC in her 40s and, thankfully, is still here. After Johnson’s doctor told her that her own chances of facing a similar fate were exceedingly high, she chose the double-mastectomy as the safer bet.

The surgery didn’t spare her, however. A post-op pathology report found that Johnson already had an aggressive type of breast cancer (“stage 1, triple-negative, grade 3”) in her right breast that required immediate treatment.

Her plastic surgeon was “adamant,” she says, that she get breast implants to return her body to normal, since she was so young. She got silicone implants on her 30th birthday. Within several months, she began experiencing intermittent, aching pain in her muscles and joints, as well as “shooting, stabbing pains” in her chest, she reports. She also battled rashes and severe fatigue. “I basically felt like I was dying a slow death, like my body was just giving out slowly over time,” she recalls.

A team of specialists told her nothing was wrong. But her symptoms continued—leaving her distraught. After four years of this, she had her implants removed (known as explant surgery). To her great relief, “I started feeling better right away,” she says. “Every single symptom disappeared within a year.”

Johnson is among those who have experienced what’s colloquially known as breast implant illness (BII), when significant health issues—fatigue, chest pain, hair loss, headaches, chills, photosensitivity, rash, chronic joint pain, among other symptoms—arise after getting implants.

[….]

We asked women who’ve undergone reconstruction or done elective breast implant surgery to share their experiences. We also polled breast health experts on their thoughts about this popular cosmetic surgery being done in the U.S. and around the world—and its potential implications for the chronic community.

SAFETY CONCERNS

Are Breast Implants Safe? Or Not?

In October 2021, the FDA issued new restrictions for breast implants, including a mandated box warning on the product label to inform patients of significant health risks, such as an increased cancer risk; a checklist of items that health care providers should discuss with patients as they consider implants; updated silicone gel-filled breast implant rupture screening recommendations; and a list of specific materials used to create the implant.

Then, this past September, the FDA issued a safety communication following reports of cancers, including squamous cell carcinoma (SCC) and various lymphomas in the scar tissue that had formed around breast implants, noting that “currently, the incidence rate and risk factors for SCC and various lymphomas in the capsule around the breast implants are unknown.” A spokesperson for the agency added, “The FDA recognizes that many patients’ symptoms may take years to develop, and patients may not be aware of the risk of SCC … We will keep the public informed as significant new information becomes available about SCC and lymphoma variants in the breast implant capsule.”

[….]

PATIENT REPORTS

Implants Remain Popular, Yet Some Patients Suffer

Safety issues haven’t dimmed enthusiasm for breast implants. According to a 2020 report by the American Society of Plastic Surgeons (ASPS), there were 137,808 implants provided for breast reconstruction and 193,073 for cosmetic surgery in this country alone. Silicone implants were used in 84% of breast augmentations, while saline implants were used in 16% of such procedures in 2020.

Mark Clemens, M.D., a professor of plastic surgery at MD Anderson in Houston, TX, who has led several MD Anderson-based safety studies on breast implants, says the recent FDA communication shouldn’t alter the perception of breast implant safety. He believes that it was done out of abundance of caution to inform, not frighten, women. When it comes to breast implants, “the vast majority of women will be completely healthy [after getting them] and won’t have any issues,” he says. However, he urges women who notice any signs of abnormality—asymmetry between breasts, the firming of a breast, or a palpable mass or a fluid collection—to consult a physician to ensure there’s nothing wrong.

Diana Zuckerman, Ph.D., president of the National Center for Health Research, a Washington, D.C.-based nonprofit organization that draws from scientific studies to improve public policy and medical oversight in the U.S., believes more independent research is required before an accurate safety assessment can be made. She says that nearly all the research being done on breast implant safety has been conducted by the very hospitals and plastic surgery organizations that either offer reconstruction and elective implant procedures as a service, or represent the surgeons who are paid to perform them—a big source of revenue and conflict of interest, leaving troubling questions of inherent bias being baked into the results.

“I can’t emphasize enough how much resistance there has been from the plastic surgeons’ medical societies and the implant manufacturers” to doing more and better research on implants, Zuckerman says. While some plastic surgeons have vocalized their concerns over the need for better information for their patients, “the medical societies—the major sources of information that FDA officials rely on—have been vehemently opposed,” she reports. “Their usual mantras are some variation of ‘breast implants are the most studied medical device in history’; hundreds of studies prove they are very safe’; and ‘so-called breast implant illness symptoms are common symptoms caused by aging and other factors, not by the implants.’” Implant manufacturers say the same thing—not coincidentally, Zuckerman adds.

Nicole Daruda, age 58 and living in Vancouver Island in Canada, openly doubts the industry’s safety claims. “Breast implants are linked to autoimmune symptoms and diseases and many other health problems,” she maintains. Daruda got cohesive gel implants in 2005 and saw her once excellent health “decimated by breast implants.” Within the first few years of having them she says she experienced fatigue, brain fog, various infections, food allergies, and hypothyroidism, with more symptoms appearing each year.

Daruda had her implants removed in 2013, and within four years she says all of her symptoms resolved. She started the Facebook group, Breast Implant Illness and Healing by Nicole, in April 2015 to provide a forum for women experiencing health issues after having implants to support and talk to each other. The group now has more than 170,000 members. Daruda says that she’s heard from thousands of women on her social media platform who report their health has improved after getting their implants removed.

[….]

IMPLANTS AND LYMPHOMA

What You Need to Know About Lymphoma

According to the FDA, as of September 2020, more than 700 people worldwide have been diagnosed with breast implant-associated anaplastic large cell lymphoma, an uncommon cancer. The agency found that the women with textured breast implants have a small but increased risk of developing this disease. The working theory, Dr. Glasberg explains, is that the texturing on the implant drives inflammation, which causes a change in the capsule around the implant that then develops into lymphoma.

Despite his belief that breast implants are safe for the vast majority of women, Dr. Clemens authored a 2021 study that examined eight cases of Epstein–Barr virus-positive large B-cell lymphoma associated with breast implants “and we’ve been trying to understand these better,” he says. (The eight women in the study were all patients at MD Anderson, a medical center that offers breast reconstruction and elective breast implant surgery, who were among the 30 known cases in the world of this type of lymphoma, per the FDA tally.) Increased awareness, combined with more pathology testing of scar tissue, plus physicians and patients being aware of breast implant-associated issues has “drawn our attention to looking for these other diseases,” he says.

IMPLANTS AND AUTOIMMUNE DISEASE

Breast Implants and Autoimmune Disease

Autoimmune issues arise when the body mistakenly attacks its own healthy tissue, causing damaging inflammation and often chronic pain and fatigue, among other symptoms, some of them disabling and/or permanent.

In 2018, MD Anderson conducted the largest study to date to explore long-term safety outcomes of breast implants, finding an association, though not a causation, with some rare diseases, including the autoimmune disorders Sjögren’s syndrome, rheumatoid arthritis (RA), and scleroderma. What’s more, researchers in the Netherlands found that more than two-thirds of women with autoimmune symptoms who had their breast implants removed experienced a reduction in symptoms.

That same year an Israeli study—research that Zuckerman says is both independent and well-designed—compared more than 24,000 breast implant patients to more than 98,000 women without breast implants but who shared similar demographic traits and reported a 22% increase in several autoimmune and rheumatic disorders, as diagnosed by their physicians and reported in their medical records. In addition, the same study reported a 60% increased risk of Sjögren’s syndrome, multiple sclerosis (MS), and sarcoidosis among those with implants, as well.

Dr. Clemens, the principal investigator of the large MD Anderson study, points out that some of those diseases in his study were self-reported by study participants, and not necessarily diagnosed by a physician—a limitation of the research. He doesn’t believe the findings are cause for concern. “The vast majority of patients with implants do not experience these symptoms or diseases,” he says. “However, it is important that they are aware of these conditions so that if they note any changes or have concerns, they can discuss with their treating physician.”

Then again, a 2021 study on breast implants and respiratory health found that 74% of participants who had their breast implants removed showed significant improvements on at least three of the six pulmonary function tests performed—an objective, not self-reported, medical tool.

For her part, Zuckerman notes that research is often funded by implant manufacturers and used to argue that breast implant illness is not real. A major weakness of most BII studies, a report by her organization found, is that they evaluate only diagnosed diseases. The reason why women decide to have their implants surgically removed and not replaced, she explains, is often due to symptoms of autoimmune and connective tissue diseases, rather than official diagnoses.

“The women and their doctors often report a constellation of symptoms that do not fit the exact criteria of known diseases,” she explains, adding that most people aren’t hospitalized for the autoimmune issues most associated with BII. Without symptoms that perfectly fit a specific diagnosis, many women will not have a diagnosis logged into medical records.

[….]

REMOVING YOUR IMPLANTS

Can Implant Removal Mean a Return to Health?

Some women, who can find no other explanation for their symptoms, like Johnson, are having their implants removed. In 2020, 22,676 explants were performed on reconstruction patients in the U.S., per the ASPS. Johnson says she was forced to find a different plastic surgeon to perform the procedure, since the one who put them in didn’t believe they caused health issues.

“He stood back looking at my chest and said, ‘I did an amazing job on those and really don’t want to take them out,’” she recalls.

[….]

Zuckerman believes the health rebound after explant surgery may be higher than the plastic surgery industry acknowledges. Since 2015, her organization has been contacted by more than 4,500 women who had breast implants they wanted removed due to rupture, breast pain, or medical symptoms caused, they believed, by their implants. NCHR was asked to advocate with health insurance companies, Medicare, and Medicaid to cover the costs of implant removal, she adds, since many of the women could not afford explant surgery.

[….]

To read the entire article, click here.

Comment of the National Center for Health Research Submitted to the EPA on the Designation of PFOA and PFOS as CERCLA Hazardous Substances, October 6, 2022

October 6, 2022

The National Center for Health Research appreciates the opportunity to provide comments on the designation of PFOA and PFOS as CERCLA hazardous substances. We are a public health think tank that conducts research, scrutinizes research conducted by others, and determines how research findings can be used to improve health policies and explains what is known and not known about the risks and benefits of specific products, programs, and policies.

For several years, we have been actively engaged in the study of the impact of PFOA, PFOS, and other PFAS chemicals on human health. There is clear evidence that these chemicals can disrupt the endocrine system in humans even at low levels.  Exposure can exacerbate such common conditions as obesity, early puberty, attention disorders, and eventually cause cancer.  We are therefore writing in strong support of the designation of PFOA and PFOS as CERCLA hazardous substances. This is an important first step because it holds companies accountable for these toxic substances, which in turn will improve public health.

Unfortunately, detailed information is lacking on most of the thousands of compounds that comprise PFAS.  Since it is unlikely that EPA can compile comprehensive toxicity data on all members of this class of chemicals, EPA should make it an urgent priority to work with independent researchers and other federal agencies to develop a common definition of PFAS, and ensure that researchers and regulatory agencies assess and restrict these chemicals as a class. PFAS classes should be determined based on exposure data, chemicals that are located or utilized together, and other parameters such as structure. Known hazards in well-studied compounds should be assumed to extrapolate to similar compounds that lack good data, until research is conducted to fill those data gaps.

In conclusion, the National Center for Health Research agrees that the designation of PFOA and PFOS as CERCLA hazardous substances is consistent with the clear evidence that these chemicals disrupt the endocrine system, accumulate in the environment and in the human body, and can cause serious health problems for humans and other animals.  Since there are thousands of other chemicals with similar structures that are not yet regulated, despite the assumption that they can cause similar harm, we strongly urge the EPA to regulate PFAS as a class of chemicals for the protection of public health and our environment.

For additional information about our work in this area, contact info@center4research.org.

Testimony of Diana Zuckerman at the Meeting of EPA’s National Environmental Justice Advisory Council on September 28, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical and consumer products, and we don’t accept funding from companies that make those products.  Our largest program is focused on cancer prevention and treatment.  My expertise is based on post-doc training in epidemiology and public health, and my previous positions at HHS and as a faculty member and researcher at Harvard and Yale.

 Thank you all for the important work you’ve been doing and will be doing on this Advisory Council.  As a public health person, I’ve always been surprised at the lack of other public health advocates who are active on environmental issues and environmental justice issues, and I want to offer to be helpful in any way that would be useful to all of you.  We all know that lives are at stake.

I want to comment very briefly on the PFAS recommendations, since that’s an issue we’ve worked on for years.  Let me add that we are very concerned about all endocrine disrupting chemicals not just PFAS.

Everything I heard about PFAS this afternoon was inspiring and important.  I would just suggest that it’s a huge task, and I encourage you to start a little smaller in order to succeed in educating the public and especially environmental justice communities and at the same time focus on actions that are doable, that will inspire others, and that will make change happen.

Testimony of Dr. Diana Zuckerman About COPIKTRA FDA Advisory Committee Meeting on September 23, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. Our largest program is focused on cancer. My expertise is based on post-doc training in epidemiology and public health, and my previous positions at HHS and as a faculty member and researcher at Harvard and Yale.

In April this same Committee examined 6 randomized trials of Pi3K inhibitors used for hematologic malignancies and found that all reduced overall survival –despite potential benefit for PFS. FDA says that these consistent findings across multiple randomized trials within the same drug class is unprecedented in oncology.
That’s a shocking finding that we need to take seriously. And that’s the context for today’s meeting.

The sponsor did a 5-year randomized controlled post-market study – 3 years longer than the data that resulted in initial approval. They found the median OS was 11 months shorter than the comparison drug. In fact, 50% of the patients died during those 5 years, compared to 44% taking the other treatment – a treatment that is no longer considered effective and so is rarely used.

Then they analyzed patients with 2 or more prior therapies, since that was the indication. Those Copiktra patients lived about 3 months shorter – not as bad as the larger sample, but still worrisome. Especially since 56% died during the 5 years of the study, compared to 49% assigned to the other treatment.

Adverse events caused the deaths of 15% of the Copiktra patients compared to only 3% of the other treatment group. And the percentage of Grade 3 or greater AEs was 91%, and 78% had Serious AEs–about twice as high as the comparison group. This has clear implications for quality of life, in addition to the patients not living as long.

The FDA did the right thing by requesting this post-market study. And the sponsor did the right thing by completing the study. Now is the time to listen to the results. We urge this Advisory Committee and the FDA to make it clear that approvals will be rescinded when evidence indicates that promising short-term results are reversed based on longer term data from post-market studies.

Patients and oncologists want as many treatment options as possible, but we do patients no favors by maintaining approval for a drug that does more harm than good. As was true yesterday for other cancer treatments, the preponderance of evidence is clear today.

As a cancer survivor myself, I understand the need for treatment options. I thank this committee and the FDA for its objective, scientific analysis of the data presented yesterday and today. I hope it will help everyone understand that an individual patient may seem to do well on a specific treatment, but that treatment may not be the REASON the patient did well. There are other individual differences that cause some patients to do better than others, and to live longer than others. As FDA stated, these diseases are often indolent. That’s why large, long-term randomized controlled trials are so important – to help us understand which treatments are better for which patients.

There are so many problems with the data, including the very substantial changes in treatment standards that have occurred since this study was designed, the low number of US patients, and the dearth of nonwhite patients – all these support rescinding approval for this indication.

It takes years for FDA to rescind approval unless the sponsor does the right thing by voluntarily doing so. But your vote today will be very influential.

I hope that the sponsor will conduct new research to determine if a subgroup of patients can benefit from this drug under current treatment standards, and if a lower dose is safer as well as effective, and if so FDA should of course consider approval for a different indication. But that isn’t where we are today.

Testimony of Dr. Diana Zuckerman About PEPAXTO FDA Advisory Committee Meeting on September 22, 2022

I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products.  Our largest program is focused on cancer.  My expertise is based on post-doc training in epidemiology and public health, and previous positions at HHS and faculty member and researcher at Yale and Harvard.

All of us want more treatment options for refractory cancers, but we want patients to be able to have confidence that FDA approval means a product is proven safe and effective.  The OCEAN study of 495 multiple myeloma patients has important information that was not available when the drug received accelerated approval. Even if some patients taking Pepaxto do well, it is only with a randomized controlled trial that we can determine if Pepaxto is helpful or if the patients would do better without it.

Our Center’s analyses support the FDA findings that the data do not confirm the indication.  In the randomized trial comparing Pepaxto to another treatment option, median survival was 5.3 months shorter, and the death rate was slightly higher.

The Sponsor says some patients do better but we agree with FDA that “Results from subgroup analyses cannot be used to conclude benefit in a subset of patients, when the overall patient population has shown a detrimental treatment effect.”

We also agree with the FDA that PFS is not improved and that “An anti-cancer therapy that prolongs PFS is not considered safe and effective if the therapy results in a detrimental effect on OS”

Public trust in the FDA has been weakened in recent years.  FDA standards matter to all of us.  Would you want your loved one to take Pepaxto rather than a superior treatment option?  Not all oncologists will be as knowledgeable about the data as those serving on this panel.

It concerns us that the sponsor continues to ignore FDA concerns, rely on shortcuts instead of better research, and that the company withdrew the drug in October but then rescinded the withdrawal.  Was this just a delaying tactic?  We agree with the FDA that the sponsor did not provide new data, and with Dr. Pazdur that FDA approval relies on solid information about appropriate dosage, which is lacking here.

Maybe Pepaxto would benefit some types of patients and better research is needed to prove that.  As FDA states, the preponderance of evidence from the prespecified analysis and in all other subgroups suggests an increased risk of death in patients and a potential for harm.”

We were pleased that the Committee voted 14-2 that the evidence does not support that the benefits outweigh the risks.

The FDA followed through and rescinded Pepaxto approval in December, 2022.

Joint Letter to Support FDA Proposed Rule Reducing Nicotine Levels in Cigarettes

September 12, 2022

Dr. Robert Califf
Commissioner
U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993

Re: Nicotine Standard

Dear Dr. Califf:

The undersigned public health, medical and professional organizations write in strong support of your recent announcement that FDA will issue a proposed rule to reduce the nicotine level in cigarettes to non-addictive or minimally addictive levels. Such a standard would generate massive public health benefits, preventing millions of young people from smoking and dramatically reducing the number of people who die from tobacco-caused diseases. We urge you to move forward with this proposal as quickly as possible.

Despite great progress in curbing smoking prevalence in recent years, tobacco use – primarily smoking – remains the leading cause of preventable death and disease in the United States, killing more than 480,000 Americans every year.1 Sixteen million Americans are currently living with a tobacco-caused disease.2 Over 30 million Americans currently smoke, and every day over 1,600 kids try their first cigarette.3 Approximately half of people who smoke will die prematurely as a result of their addiction, losing at least a decade of life on average compared to those who do not smoke.4

We applaud the Administration for taking action to reduce tobacco use as part of its Cancer Moonshot initiative.5 Cigarette smoking causes about 30 percent of all cancer deaths in the U.S.6 Reductions in tobacco use have already had an impact on cancer rates. According to CDC, 60 percent of the decrease in cancer death rates among men and 40 percent of the decrease among women from their peak in 1990 to 1991 until 2014 were due to declines in tobacco-related cancer deaths.7 More progress can be made and reducing nicotine levels will have a profound impact.

Nicotine is the primary addictive agent in cigarettes and other tobacco products. According to the U.S. Surgeon General, “the addiction caused by the nicotine in tobacco smoke is critical in the transition of smokers from experimentation to sustained smoking and, subsequently, in the maintenance of smoking for the majority of smokers who want to quit.”8 Thus, reducing the nicotine content in cigarettes to non-addictive or minimally addictive levels will prevent experimentation by the young from becoming a lifetime of addiction and tobacco-caused disease. It also will reduce the level of nicotine dependence in adults who smoke, making it easier for them to quit.

Current evidence establishes the potentially historic lifesaving impact of reducing nicotine content in cigarettes to non-addictive or minimally addictive levels. As you know, FDA estimated in 2018 that approximately 5 million additional adults who smoke could quit smoking within one year of implementation and, by the year 2100, more than 33 million people – mostly youth and young adults – would have avoided becoming regular smokers. Smoking rates could drop to as low as 1.4 percent, resulting in more than 8 million fewer tobacco-caused deaths through the end of the century.9 The dimensions of this public health benefit make timely implementation of this policy a moral imperative.

Reducing nicotine levels in cigarettes to achieve these enormous public health gains is technologically feasible. As FDA noted in its earlier Advance Notice of Proposed Rulemaking (ANPRM), there are a wide range of available technologies to reduce nicotine in cigarettes, including “through tobacco blending and cross-breeding plants, genetic engineering, and chemical extraction.”10 Indeed, the tobacco industry’s own documents show that the industry has a long history of manipulating nicotine levels in cigarettes to make them more addictive. As U.S. District Court Judge Gladys Kessler determined in her landmark opinion finding that the major cigarette companies had violated the federal anti-racketeering statute, “Defendants have designed their cigarettes to precisely control nicotine delivery levels and provide doses of nicotine sufficient to create and sustain addiction.”11 Surely the companies cannot now credibly maintain that they are unable to reduce nicotine levels to no longer sustain addiction. In addition, FDA has noted that recent scientific studies do not support concerns that nicotine reduction would cause people who smoke to compensate by increasing the number of cigarettes smoked or inhaling more deeply to increase nicotine intake. Studies of very low nicotine cigarettes have not found evidence of compensatory smoking but have found demonstrable reductions in cigarettes smoked per day and in exposure to harmful smoking constituents.12

To realize the full potential public health benefits of a nicotine product standard, FDA must extend that standard beyond cigarettes, to other combustible tobacco products. Exempting other combustible products would invite tobacco manufacturers to market existing, or develop new, non-cigarette substitutes, like the small, flavored cigars the industry introduced after flavored cigarettes (except menthol) were removed from the market. It also would make the exempted products a potential vehicle for youth initiation. Thus, we urge FDA to make any nicotine reduction product standard applicable to other combustible tobacco products.

Reducing nicotine in cigarettes and other combusted tobacco products will complement FDA’s proposed rules to prohibit menthol cigarettes and flavored cigars. By addressing flavors and nicotine levels, FDA will be able to target both what attracts youth to these products and what addicts them. FDA should continue its work to promptly finalize and implement the menthol cigarette and flavored cigar proposed rules. Moreover, FDA should continue to address high rates of e-cigarette use by youth by promptly completing statutorily required premarket reviews and removing from the market those products that are not “appropriate for the protection of the public health.”

Reducing the nicotine content in cigarettes and other combustible tobacco products will dramatically reduce addiction, disease, and premature death from tobacco. We applaud FDA for setting forth a bold plan to protect kids and public health and urge the agency to act quickly to complete the rulemaking process. Every day that passes means more kids moving from experimentation to addiction and more adults who want to quit, and try to quit, but remain addicted to a lethal product.

Respectfully submitted,

AASA, The School Superintendents Association
Academy of General Dentistry
Action on Smoking and Health
Allergy & Asthma Network
Alpha-1 Foundation
American Academy of Family Physicians
American Academy of Oral and Maxillofacial Pathology
American Association for Cancer Research
American Association for Dental, Oral, and Craniofacial Research
American Association for Respiratory Care
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Physicians
American Dental Association
American Heart Association
American Public Health Association
American Society of Addiction Medicine
Americans for Nonsmokers’ Rights
Association for Clinical Oncology
Association for the Treatment of Tobacco Use & Dependence
Association of Black Cardiologists
Association of State and Territorial Health Officials
Asthma and Allergy Foundation of America
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Catholic Health Association of the United States
Center For Black Equity
Children’s Health Fund
Commissioned Officers Association of the USPHS
Common Sense Media
Community Anti-Drug Coalitions of America (CADCA)
COPD Foundation
Counter Tools
Dana-Farber Cancer Institute
Emphysema Foundation of America
Family, Career and Community Leaders of America (FCCLA)
First Focus on Children
GLMA: Health Professionals Advancing
LGBTQ+ Equality
GO2 Foundation for Lung Cancer
HealthHIV
International Association for the Study of Lung Cancer
Kaiser Permanente
March of Dimes
National Alliance to Advance Adolescent Health
National Association of Hispanic Nurses
National Association of Pediatric Nurse Practitioners
National Association of School Nurses
National Association of Secondary School Principals
National Black Church Initiative
National Black Nurses Association
National Education Association
National Hispanic Medical Association
National LGBT Cancer Network
National Medical Association
National Native Network
National Network of Public Health Institutes
National Tongan American Society
North American Quitline Consortium
Oncology Nursing Society
Parents Against Vaping e-cigarettes (PAVe)
Preventing Tobacco Addiction
Foundation/Tobacco 21
Preventive Cardiovascular Nurses Association
Respiratory Health Association
SADD
Society for Cardiovascular Angiography & Interventions
The Center for Black Health and Equity
The Society for State Leaders of Health
and Physical Education
The Society of Thoracic Surgeons
Trust for America’s Health
Truth Initiative
US COPD Coalition

CC: Dr. Brian King, Director of the Center for Tobacco Products

1. HHS, The Health Consequences of Smoking – 50 Years of Progress: A Report of the Surgeon General, 2014 (2014 SG Report).
2. Id.
3. CDC, “Tobacco Product Use Among Adults—United States, 2020,” MMWR Morb Mortal Wkly Rep
2022;71:397–405, March 18, 2022, https://www.cdc.gov/mmwr/volumes/71/wr/mm7111a1.htms_cid=mm7111a1_w. Substance Abuse and Mental Health Services Administration (SAMHSA), HHS, Results from the 2019 National Survey on Drug Use and Health, NSDUH: Detailed Tables, Table 4.9A https://www.samhsa.gov/data/report/2019-nsduh-detailed-tables
4. 2014 SG Report
5. The White House, “President Biden Reignites Cancer Moonshot to End Cancer as We Know It,” Fact Sheet. February, 2, 2022, https://www.whitehouse.gov/briefing-room/statements-releases/2022/02/02/fact-sheet-president-
biden-reignites-cancer-moonshot-to-end-cancer-as-we-know-it/
6. American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society, 2022.
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html
7. CDC, “Vital Signs: Disparities in Tobacco-Related Cancer Incidence and Mortality—United States, 2004-2013,” MMWR 65(44): 1212-1218, https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6544a3.pdf/.
8. 2014 SG Report.
9. Apelberg, BJ, et al., “Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States,” New England Journal of Medicine, published online March 15, 2018. See also, “Tobacco Product Standard for Nicotine Level of Combusted Cigarettes,” Advance Notice of Proposed Rulemaking, 83 Fed. Reg. 11818, 11820 (March 16, 2018)(ANPRM)
10. ANPRM, at 11820.
11. U.S. v. Philip Morris, Inc., 449 F.Supp. 2d, 1, 309 (D.D.C. 2006), aff’d in relevant part. 566 F.3d 1095 (D.C. Cir.2009).
12. ANPRM, at 11820.

Liver Cancer: What is it and how to prevent it


An estimated 100,000 people live with liver cancer in the U.S.[1] with about 41,000 new cases each year.2 Although less common than many other cancers in the U.S., the rate of newly diagnosed liver cancer has tripled since 1980 and death rates have doubled.[2]  It is often diagnosed in late stages and when it is, the average survival after diagnosis is less than 4 months at stage 4, compared to more than 3 years at the earliest stage.[3]

Early diagnosis and reducing the risks of developing liver cancer would save thousands of lives each year.  Research indicates that liver cancer disproportionality affects Asian American and Pacific Islander (AAPI) communities, which is the fasted growing racial and ethnic minority in the US.[4] Asian Americans are almost twice as likely to be diagnosed with liver cancer than Non-Hispanic White Americans, and in 2019, liver cancer was the sixth leading cause of death among 25-44 year old Asian Americans.[5] A better understanding of those disparities could save many lives.

This article will explain the signs and symptoms of liver cancer and the steps you can take to prevent it. 

Symptoms and Outcomes of Liver Cancer

Many symptoms of liver cancer are also symptoms of liver damage, [6]which can include:

  • Jaundice (yellowing of the skin or the whites of the eyes)
  • Pain in the right abdomen or shoulder blade
  • Lump in your right abdomen

However, liver cancer can also result in symptoms that are typical of other illnesses:[7]

  • Weight or appetite loss
  • Nausea or vomiting
  • General weakness or fatigue 

Primary liver cancer refers to cancer that originates in the liver, and is usually a single large tumor, whereas liver cancer that originates from another region of the body but spreads to the liver is called liver metastases and usually consists of several small tumors.[6] Liver metastases are more common than primary liver cancer and may spread throughout the liver before they are detected, while primary liver cancer can cause symptoms very early.[6,8]

How can you prevent it? 

There are several things you can do to reduce your chances of developing primary liver cancer.

Get tested for Hepatitis C: Approximately half of all primary liver cancer can be attributed to a single cause: the Hepatitis C virus.[9] The virus causes inflammation to the liver, which can lead to scarring (or ‘cirrhosis’) and then ultimately to liver cancer. You can contract Hepatitis C by being in contact with the blood of an infected person, so injecting drugs. is the most common way the virus is spread in the U.S.[10] The virus may silently damage the livers of infected people for decades before any symptoms appear. In fact, about half of people with Hepatitis C don’t even know they are infected.[11] Of the 3.5 million Americans estimated to be infected with Hepatitis C, 81% are baby boomers who were likely infected before Hepatitis C was discovered in 1989.[9]

Since Hepatitis C often has no symptoms, it’s crucial to get tested. The CDC recommends that all adults get tested for Hepatitis C at least once in their life, and all pregnant women get tested during every pregnancy.[12] Persons who inject drugs or share needles should get tested regularly.[12]

Get vaccinated for Hepatitis B: Hepatitis B is thought to cause about 15% of Liver cancer cases in the U.S. Like Hepatitis C, Hepatitis B attacks the liver, and most people who have been infected don’t realize it.[13] While about 1 million more Americans are living with Hepatitis C than B,[13] Hepatitis B is 5-10 times more infectious and is most commonly spread from mother to child during birth.[14] It is also more commonly transmitted through sexual activity than Hepatitis C.[15] Fortunately, Hepatitis B can be prevented with a vaccine, while Hepatitis C currently cannot. The Hepatitis B vaccine is usually given as a series of 3 shots shortly after birth, 1-2 months after birth, and 6-18 months after birth.[16] As of 2022, the CDC recommends all unvaccinated children and adults age 19-59 receive the Hepatitis B vaccine.[17] 

Asian American and Pacific Islanders make up approximately half of all Americans currently infected with Hepatitis B, despite making up only 6% of the U.S. population. That is likely because Hepatitis B has circulated around many countries in East Asia, Southeast Asia, and the Pacific for thousands of years, and also because these regions have very low rates of infant Hepatitis B vaccinations.[18]

Get treated for Hepatitis B or C: There are many treatment options for chronic Hepatitis C that can reduce its viral load to an undetectable level and help prevent cancer-causing liver damage. Antiviral medications are one of the most common ways treat the virus. FDA has approved several antiviral medications for the treatment of either Hepatitis B or C in the US, and there continue to be new advances in treatment options. These antiviral medications may vary in terms of safety or effectiveness. For example,  information about two of the most widely used Hepatitis B antivirals (Baraclude and Vemildy) and Hepatitis C antivirals (Mavyret and Epclusa) are shown in the table below.[19,20] FDA has approved all these drugs as having benefits that outweigh the risks in treating Hepatitis B or C, but your doctor may suggest specific medications based on your Hepatitis diagnosis, preexisting conditions, and other health factors.

Name of antiviral Description and usage Unique advantages Side Effects (including % of patients who experience them)
Baraclude (Entecavir) Pill usually taken once a day for many months and up to a year or more to treat Hepatitis B. Shown to be more effective for those with resistance to other Hepatitis B drugs such as lamivudine or adefovir.19 Common

  • Liver Cancer (10-12%)21 
  • Low albumin in the blood, which can cause swelling, weakness, fatigue, or cramps (10-30%)21,22
  • Increases the risk of dangerous bleeding by lowering the platelets in the blood (10-20%)21,23
  • Elevated lipase, which may indicate disease of the pancreas (10-18%)21,24
  • Swelling in your lower legs or hands (10-16%)21

Rare / Serious

  • Kidney failure (0.1-1%)21
  • Lactic acid buildup, which can be fatal ^ 25

Enlarged liver^ 25

Vemlidy (Tenofovir alafenamide) Pill usually taken once a day for many months and up to a year or more to treat Hepatitis B. Very similar advantages to Entecavir when compared to other drugs.19 Research is needed to directly compare this drug with Entecavir to see if one is more effective than the other.19 Common

  • Headache (1-12%)26
  • Abdominal pain (1-10%)26
  • Nausea (1-10%)26
  • Fatigue (1-10%)26        
  • Rash (1-10%)26

Rare / Serious

  • Lactic acid buildup, which can be fatal ^ 27
  • Enlarged liver^ 27
Mavyret (Glecaprevir and Pibrentasvir) Pill usually taken once a day for 8-16 weeks to treat Hepatitis C. Only drug approved by FDA for a shorter 8-week treatment period instead of the usual 12-week period for other drugs.28 Common

  • Headache (10-17%)29
  • Itchy skin (10-17%)29
  • Fatigue (10-16%)29
  • Nausea (10-12%)29

Rare / Serious

  • Reactivation of Hepatitis B (for those co-infected) ^ 30
  • Allergic reaction (which can cause swelling or difficulty breathing) ^ 30
Epclusa (Sofosbuvir and Velpatasvir) Pill usually taken once a day for 12 weeks to treat Hepatitis C. Only drug approved to treat Hepatitis C in children as young as 6 years old.31 It is also the first medication to treat all 6 Hepatitis C genotypes.20  Common

  • Fatigue (10-32%)32
  • Headache (10-29%)32
  • Anemia (10-26%)32
  • Nausea (10-15%)32

Rare / Serious

  • Reactivation of Hepatitis B (for those co-infected) ^ 33
  • Allergic reaction (which can cause swelling or difficulty breathing) ^ 33

^ frequency not reported

Avoid alcohol and smoking: Alcohol is well known to damage the liver; an analysis of 112 studies found that consuming an average of just one alcoholic drink a day was associated with a 10% greater chance of developing liver cancer.[34] The annual average is of 9.5 new cases and 6.6 deaths from liver cancer for every 100,000 adults in the U.S.,[1] but a review of 28 studies that analyzed almost 5,000 new cases of liver cancer and more than 10,000 liver cancer deaths found that moderate and heavy drinkers (at least 1 drink/day for females and at least 2 drinks/day for males) were 42% more likely to be diagnosed with liver cancer and 17% more likely to die from it.[35] 

Smoking also significantly increases the chance of developing liver cancer. A 2018 study of more than 1 million Americans found that current smokers were 86% more likely to be diagnosed with liver cancer than non-smokers. Fortunately, the study also found that individuals who quit smoking at least 30 years ago had the same risk of liver cancer as those who had never smoked, suggesting that younger smokers who decide to quit smoking now can significantly reduce their future risk of developing liver cancer.

Maintain a healthy weight: Studies consistently show that being overweight or obese increases the risk of developing liver cancer;[36] In one analysis of 11 different studies, even after most studies controlled for the effects of age, sex, smoking, and other health conditions, being overweight (BMI between 25-30) increased the risk of liver cancer by 17%, while being obese (BMI 30 or above) increased the risk by 89%.[37] For example, one of the studies, of more than 780,000 Korean men, found a rate of liver cancer of 43 out of every 100,000 for men with a healthy weight (BMI 18.5-25), compared to 66 for every 100,000 for men who were obese.[38] This may be because fat tissue that accumulates in the liver can cause damaging inflammation, which may then lead to liver cancer.[36]

Taking steps to maintain a healthy weight through diet and exercise can therefore reduce the chances of developing liver cancer. An important question is whether losing weight through bariatric surgery also reduces the chances of developing liver cancer.[36] For example, in a study of 190 morbidly obese individuals with non-alcoholic steatohepatitis (a type of fatty liver disease that increases the risk of liver cancer), 85% were rid of the disease one year after bariatric surgery.[39] However, more long-term research is needed to investigate whether bariatric surgery reduces the risk of liver cancer or whether other factors are influencing those better outcomes.[36] For example, in a 2022 study, more than 5,000 adults with obesity who received bariatric surgery and more than 25,000 patients who received nonsurgical care were followed for an average of 6 years. While bariatric surgery patients had a lower rate of liver cancer (9 versus 15 cases per 100,000 people per year), this difference was not statistically significant when adjusted for other factors such as age, sex, smoking status, and medication use.[40]  That means that the differences were probably due to those other traits, not to the bariatric surgery itself.

References:

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  2. Key Statistics About Liver Cancer. Accessed August 4, 2022. https://www.cancer.org/cancer/liver-cancer/about/what-is-key-statistics.html
  3. Survival | Liver cancer | Cancer Research UK. Accessed August 9, 2022. https://www.cancerresearchuk.org/about-cancer/liver-cancer/survival
  4. Budiman A, Ruiz NG. Key facts about Asian Americans, a diverse and growing population. Pew Research Center. Published 2021. Accessed December 16, 2021. https://www.pewresearch.org/fact-tank/2021/04/29/key-facts-about-asian-americans/
  5. Chronic Liver Disease and Asian Americans – The Office of Minority Health. Accessed August 4, 2022. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=47
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  19. Chen LP, Zhao J, Du Y, et al. Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma. World J Virol. 2012;1(6):174-183. doi:10.5501/wjv.v1.i6.174
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  23. Thrombocytopenia (low platelet count) – Symptoms and causes. Mayo Clinic. Accessed August 12, 2022. https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293
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  29. Mavyret Side Effects: Common, Severe, Long Term. Drugs.com. Accessed August 10, 2022. https://www.drugs.com/sfx/mavyret-side-effects.html
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  31. Commissioner O of the. FDA Approves New Treatment for Pediatric Patients with Any Strain of Hepatitis C. FDA. Published March 24, 2020. Accessed August 5, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pediatric-patients-any-strain-hepatitis-c
  32. Epclusa Side Effects: Common, Severe, Long Term. Drugs.com. Accessed August 10, 2022. https://www.drugs.com/sfx/epclusa-side-effects.html
  33. Epclusa: Side effects, for hepatitis C, dosage, and more. Published June 30, 2022. Accessed August 10, 2022. https://www.medicalnewstoday.com/articles/326248
  34. Chuang SC, Lee YCA, Wu GJ, Straif K, Hashibe M. Alcohol consumption and liver cancer risk: a meta-analysis. Cancer Causes Control. 2015;26(9):1205-1231. doi:10.1007/s10552-015-0615-3
  35. Park H, Shin SK, Joo I, Song DS, Jang JW, Park JW. Systematic Review with Meta-Analysis: Low-Level Alcohol Consumption and the Risk of Liver Cancer. Gut Liver. 2020;14(6):792-807. doi:10.5009/gnl19163
  36. Saitta C, Pollicino T, Raimondo G. Obesity and liver cancer. Annals of Hepatology. 2019;18(6):810-815. doi:10.1016/j.aohep.2019.07.004
  37. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007;97(7):1005-1008. doi:10.1038/sj.bjc.6603932
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