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Tag: Liver Disease

  • Safety Board: Mechanical defect caused Ohio train wreck

    Safety Board: Mechanical defect caused Ohio train wreck

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    EAST PALESTINE, Ohio — A mechanical issue with a rail car axle caused the fiery derailment of dozens of freight cars in Ohio near the Pennsylvania state line Friday night, federal investigators announced Sunday. The smoldering tangle of cars, some carrying hazardous materials, kept an evacuation order in effect.

    Michael Graham, a board member of the National Transportation Safety Board, said at a news conference that the three-member train crew received an alert about the mechanical defect “shortly before the derailment” but said the board was still working to determine which rail car experienced the issue.

    About 50 cars derailed in East Palestine at about 9 p.m. Friday as a train was carrying a variety of products from Madison, Illinois, to Conway, Pennsylvania, rail operator Norfolk Southern said. No injuries to crew, residents or first responders have been reported.

    Graham said investigators also have identified the exact “point of derailment” but did not disclose the location Sunday. He said information will be included in a preliminary investigative report expected in the next month or so.

    East Palestine officials said Sunday that emergency responders were monitoring but keeping their distance from the fire, saying remediation efforts could not begin as long as the cars smoldered. The evacuation covers a 1-mile (1.6-kilometer) radius, as environmental authorities warily watch air quality monitors, officials said.

    Mayor Trent Conaway, who declared a state of emergency in the village, said one person was arrested for going around barricades right up to the crash during the night. He warned that more arrests would follow if people did not to stay away.

    “I don’t know why anybody would want to be up there; you’re breathing toxic fumes if you’re that close,” he said, stressing that monitors of air quality away from the fire showed no levels of concern and the town’s water is safe because it is fed by groundwater unaffected by some material that went into streams. Environmental protection agency crews were working to remove contaminants from streams and monitor water quality.

    Fire Chief Keith Drabick said it was so important to avoid the area “because a train carrying hazardous material wrecked in the town and is burning. Doesn’t get any simpler than that.”

    Sheriffs went door-to-door Sunday to count residents remaining and urge people within the evacuation area to leave. “We are asking residents to please evacuate and cooperate,” officials said in a statement. Schools and village offices will be closed Monday and officials would determine that afternoon whether the school closure would be extended. Businesses within the evacuation zone would not be allowed to open Monday, officials said.

    Norfolk Southern said 20 of the more than 100 cars were classified as carrying hazardous materials — defined as cargo that could pose any kind of danger “including flammables, combustibles, or environmental risks.” Some cars carried vinyl chloride, and at least one was “intermittently releasing” its contents via a pressure release device.

    Officials said Sunday afternoon that cars involved also carried combustible liquids, butyl acrylate and residue of benzene from previous shipments, as well as nonhazardous materials such as wheat, plastic pellets, malt liquors and lube oil.

    “Short-term exposure to low levels of substances associated with the derailment does not present a long-term health risk to residents,” according to a “Frequently Asked Questions” post on the village Facebook page. “Vinyl chloride and benzene may cause cancer in people exposed in the workplace to high concentrations for many years; however, there is no indication that any potential exposure that occurred after the derailment increases the risk of cancer or any other long-term health effects in community members.”

    The NTSB said only 10 cars carrying hazardous materials derailed and five of them were carrying vinyl chloride, not 14 as was said earlier. And officials stressed again late Saturday that they had not confirmed the release of vinyl chloride other than from pressure release devices operating as designed.

    Vinyl chloride, used to make the polyvinyl chloride hard plastic resin in a variety of plastic products, is associated with increased risk of liver cancer and other cancers, according to the federal government’s National Cancer Institute. Norfolk Southern was to provide a fact sheet listing all chemicals involved.

    The evacuation order covered homes of 1,500 to 2,000 of the town’s 4,800 to 4,900 residents, but officials said it was unknown exactly how many were actually affected. About eight residents remained at an emergency shelter. Norfolk Southern opened an assistance center in the village to gather information from affected residents; village officials said 75 people went to the center Saturday and about 100 had been there Sunday morning.

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  • Evacuations urged in Ohio town as train wreck smolders

    Evacuations urged in Ohio town as train wreck smolders

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    EAST PALESTINE, Ohio — A smoldering tangle of dozens of derailed freight cars, some carrying hazardous materials, has kept an evacuation order in effect in Ohio near the Pennsylvania state line as environmental authorities warily watch air quality monitors.

    About 50 cars derailed in East Palestine at about 9 p.m. Friday as a train was carrying a variety of products from Madison, Illinois, to Conway, Pennsylvania, rail operator Norfolk Southern said. No injuries to crew, residents or first responders have been reported.

    East Palestine officials said Sunday that emergency responders were monitoring but keeping their distance from the fire, saying remediation efforts could not begin as long as the cars smoldered. The evacuation covers a a 1-mile (1.6-kilometer) radius, officials said.

    Mayor Trent Conaway, who declared a state of emergency in the village, said one person was arrested for going around barricades right up to the crash during the night. He warned that more arrests would follow if people did not to stay away.

    “I don’t know why anybody would want to be up there; you’re breathing toxic fumes if you’re that close,” he said, stressing that monitors of air quality away from the fire showed no levels of concern and the town’s water is safe because it is fed by groundwater unaffected by some material that went into streams. Environmental protection agency crews were working to remove contaminants from streams and monitor water quality.

    Fire Chief Keith Drabick said it was so important to avoid the area “because a train carrying hazardous material wrecked in the town and is burning. Doesn’t get any simpler than that.”

    Sheriffs went door-to-door Sunday to count residents remaining and urge people within the evacuation area to leave. “We are asking residents to please evacuate and cooperate,” officials said in a statement. Schools and village offices will be closed Monday and officials would determine that afternoon whether the school closure would be extended. Businesses within the evacuation zone would not be allowed to open Monday, officials said.

    Norfolk Southern said 20 of the more than 100 cars were classified as carrying hazardous materials — defined as cargo that could pose any kind of danger “including flammables, combustibles, or environmental risks.” Some cars carried vinyl chloride, and at least one was “intermittently releasing” its contents via a pressure release device.

    Officials said Sunday afternoon that cars involved also carried combustible liquids, butyl acrylate and residue of benzene from previous shipments as well as nonhazardous materials such as wheat, plastic pellets, malt liquors and lube oil.

    “Short-term exposure to low levels of substances associated with the derailment does not present a long-term health risk to residents,” said a “Frequently Asked Questions” post on the village Facebook page. “Vinyl chloride and benzene may cause cancer in people exposed in the workplace to high concentrations for many years; however, there is no indication that any potential exposure that occurred after the derailment increases the risk of cancer or any other long-term health effects in community members.”

    The National Transportation Safety Board said only 10 cars carrying hazardous materials derailed and five of them were carrying vinyl chloride, not 14 as was said earlier. And officials stressed again late Saturday that they had not confirmed the release of vinyl chloride other than from pressure release devices operating as designed.

    Vinyl chloride, used to make the polyvinyl chloride hard plastic resin in a variety of plastic products, is associated with increased risk of liver cancer and other cancers, according to the federal government’s National Cancer Institute. Norfolk Southern was to provide a fact sheet listing all chemicals involved.

    The evacuation order covered homes of 1,500 to 2,000 of the town’s 4,800 to 4,900 residents, but officials said it was unknown exactly how many were actually affected. About eight residents remained at an emergency shelter. Norfolk Southern opened an assistance center in the village to gather information from affected residents; village officials said 75 people went to the center Saturday and about 100 had been there Sunday morning.

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  • AASLD Hepatology Award with Harold Amos Medical Faculty Development Program

    AASLD Hepatology Award with Harold Amos Medical Faculty Development Program

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    Newswise — In support of our unwavering commitment to champion diversity, equity, and inclusion in the field of hepatology, AASLD is pleased to announce the development of our own hepatology award. We have partnered with the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program (AMFDP), a program that provides research funding for postdoctoral scholars from historically marginalized backgrounds, to provide funding that will directly support a URM faculty hepatologist. With AASLD’s contribution, the program aims to increase the number of scholars from underrepresented groups in the field of hepatology with academic and research appointments. 

    The selected scholar will receive a $75,000 research stipend and $30,000 in research support, annually for 4 years. Additionally, support will be provided from a National Advisory Committee mentor for the duration of the award. Applications open February 8th and the deadline to submit is March 15, 2023 at 3:00 p.m. (Eastern).

    Visit the Harold Amos Medical Faculty Development Program website for full application information. 

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    American Association for the Study of Liver Diseases (AASLD)

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  • Consumption of fast food linked to liver disease

    Consumption of fast food linked to liver disease

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    Newswise — LOS ANGELES — The new year has begun, and with it, resolutions for change.

    A study from Keck Medicine of USC published today in Clinical Gastroenterology and Hepatology gives people extra motivation to reduce fast-food consumption.

    The study found that eating fast food is associated with nonalcoholic fatty liver disease, a potentially life-threatening condition in which fat builds up in the liver.

    Researchers discovered that people with obesity or diabetes who consume 20% or more of their daily calories from fast food have severely elevated levels of fat in their liver compared to those who consume less or no fast food. And the general population has moderate increases of liver fat when one-fifth or more of their diet is fast food.

    “Healthy livers contain a small amount of fat, usually less than 5%, and even a moderate increase in fat can lead to nonalcoholic fatty liver disease,” said Ani Kardashian, MD, a hepatologist with Keck Medicine and lead author of the study. “The severe rise in liver fat in those with obesity or diabetes is especially striking, and probably due to the fact that these conditions cause a greater susceptibility for fat to build up in the liver.”

    While previous research has shown a link between fast food and obesity and diabetes, this is one of the first studies to demonstrate the negative impact of fast food on liver health, according to Kardashian.

    The findings also reveal that a relatively modest amount of fast food, which is high in carbohydrates and fat, can hurt the liver. “If people eat one meal a day at a fast-food restaurant, they may think they aren’t doing harm,” said Kardashian. “However, if that one meal equals at least one-fifth of their daily calories, they are putting their livers at risk.”

    Nonalcoholic fatty liver disease, also known as liver steatosis, can lead to cirrhosis, or scarring of the liver, which can cause liver cancer or failure. Liver steatosis affects over 30% of the U.S. population.

    Kardashian and colleagues analyzed the most recent data from the nation’s largest annual nutritional survey, the 2017-2018 National Health and Nutrition Examination Survey, to determine the impact of fast-food consumption on liver steatosis.

    The study characterized fast food as meals, including pizza, from either a drive-through restaurant or one without wait staff.

    The researchers evaluated the fatty liver measurement of approximately 4,000 adults whose fatty liver measurements were included in the survey and compared these measurements to their fast-food consumption.

    Of those surveyed, 52% consumed some fast food. Of these, 29% consumed one-fifth or more daily calories from fast food. Only this 29% of survey subjects experienced a rise in liver fat levels.

    The association between liver steatosis and a 20% diet of fast food held steady for both the general population and those with obesity or diabetes even after data was adjusted for multiple other factors such as age, sex, race, ethnicity, alcohol use and physical activity.

    “Our findings are particularly alarming as fast-food consumption has gone up in the last 50 years, regardless of socioeconomic status,” said Kardashian. “We’ve also seen a substantial surge in fast-food dining during the COVID-19 pandemic, which is probably related to the decline in full-service restaurant dining and rising rates of food insecurity. We worry that the number of those with fatty livers has gone up even more since the time of the survey.”

    She hopes the study will encourage health care providers to offer patients more nutrition education, especially to those with obesity or diabetes who are at higher risk of developing a fatty liver from fast food. Currently, the only way to treat liver steatosis is through an improved diet.

    Jennifer Dodge, MPH, assistant professor of research medicine and population and public health sciences at the Keck School of Medicine of USC and Norah Terrault, MD, MPH, a Keck Medicine gastroenterologist and division chief of gastroenterology and liver diseases at the Keck School, were also authors on the study.

     

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    For more information about Keck Medicine of USC, please visit news.KeckMedicine.org.

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    Keck Medicine of USC

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  • Research shows fatty liver disease endangers brain health

    Research shows fatty liver disease endangers brain health

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    Newswise — In a study examining the link between non-alcoholic fatty liver disease (NAFLD) and brain dysfunction, scientists at the Roger Williams Institute of Hepatology, affiliated to King’s College London and the University of Lausanne, found an accumulation of fat in the liver causes a decrease in oxygen to the brain and inflammation to brain tissue – both of which have been proven to lead to the onset of severe brain diseases. 

    NAFLD affects approximately 25% of the population and more than 80% of morbidly obese people. Several studies have reported the negative effects of an unhealthy diet and obesity can have on brain function however this is believed to be the first study that clearly links NAFLD with brain deterioration and identifies a potential therapeutic target. 

    The research, conducted in collaboration with Inserm (the French National Institute of Health and Medical Research) and the University of Poitiers in France, involved feeding two different diets to mice. Half of the mice consumed a diet with no more than 10% fat in their calorie intake, while the other half’s calorie intake contained 55% fat; intended to resemble a diet of processed foods and sugary drinks. 

    After 16 weeks researchers conducted a series of tests to compare the effects of these diets on the body and more specifically, on the liver and the brain. They found that all mice consuming the higher levels of fat were considered obese, and developed NAFLD, insulin resistance and brain dysfunction.  

    The study which was funded by the University of Lausanne and Foundation for Liver Research also showed that the brain of mice with NAFLD suffered from lower oxygen levels. This is because the disease affects the number and thickness of the brain blood vessels, which deliver less oxygen to the tissue, but also due to specific cells consuming more oxygen while the brain is becoming inflamed. These mice were also more anxious and showed signs of depression. 

    By comparison, the mice consuming the healthy diet did not develop NAFLD or insulin resistance, they behaved normally, and their brain was completely healthy.  

    “It is very concerning to see the effect that fat accumulation in the liver can have on the brain, especially because it often starts off mild and can exist silently for many years without people knowing they have it,” said lead author Dr Anna Hadjihambi, sub-team lead in the Liver-Brain Axis group at the Roger Williams Institute of Hepatology and honorary lecturer at King’s College London.  

    To try and combat the dangerous effect that NAFLD has on the brain, the scientists bred mice with lower levels of a whole-body protein known as Monocarboxylate Transporter 1 (MCT1) – a protein specialised in the transport of energy substrates used by various cells for their normal function. 

    When these mice were fed the same unhealthy fat- and sugar-rich diet as those in the initial experiment, they had no fat accumulation in the liver and exhibited no sign of brain dysfunction – they were protected from both ailments. 

    “Identifying MCT1 as a key element in the development of both NAFLD and its associated brain dysfunction opens interesting perspectives,” said Professor Luc Pellerin, director of the Inserm U1313 research unit at the University of Poitiers in France and senior researcher in the study. “It highlights potential mechanisms at play within the liver-brain axis and points to a possible therapeutic target.” 

    Dr Hadjihambi added: “This research emphasises that cutting down the amount of sugar and fat in our diets is not only important for tackling obesity, but also for protecting the liver to maintain brain health and minimise the risk of developing conditions like depression and dementia during ageing, when our brain becomes even more fragile. 

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    King’s College London

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  • Famed LA mountain lion euthanized following health problems

    Famed LA mountain lion euthanized following health problems

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    LOS ANGELES — P-22, the celebrated mountain lion that took up residence in the middle of Los Angeles and became a symbol of urban pressures on wildlife, was euthanized Saturday after dangerous changes in his behavior led to examinations that revealed worsening health and injuries likely caused by a car.

    Officials with the California Department of Fish and Wildlife said the decision to euthanize the beloved big cat was made after veterinarians determined it had a skull fracture and chronic illnesses including a skin infection and diseases of the kidneys and liver.

    “His prognosis was deemed poor,” said the agency’s director, Chuck Bonham, who fought back tears during a news conference announcing the cougar’s death. “This really hurts … it’s been an incredibly difficult several days.”

    The animal became the face of the campaign to build a wildlife crossing over a Los Angeles-area freeway to give big cats, coyotes, deer and other wildlife a safe path to the nearby Santa Monica Mountains, where they have room to roam.

    Seth Riley, wildlife branch chief with the National Park Service, called P-22 “an ambassador for his species,” with the wildlife bridge a symbol of his lasting legacy.

    State and federal wildlife officials announced earlier this month that they were concerned that P-22 “may be exhibiting signs of distress” due in part to aging, noting the animal needed to be studied to determine what steps to take.

    The aging mountain was captured in a residential backyard in the trendy Los Feliz neighborhood of Los Angeles on Dec. 12, a month after killing a Chihuahua on a dogwalker’s leash. An anonymous report that indicated P-22 may have been struck by a vehicle was confirmed by a CT scan that revealed injuries to his head and torso, wildlife officials said.

    State authorities determined that the only likely options were euthanasia or confinement in an animal sanctuary — a difficult prospect for a wild lion.

    P-22 was believed to be 12 years old, longer-lived than most wild male mountain lions.

    His name was his number in a National Park Service study of the challenges the wide-roaming big cats face in habitat fragmented by urban sprawl and hemmed in by massive freeways that are not only dangerous to cross but are also barriers to the local population’s genetic diversity.

    The cougar was regularly recorded on security cameras strolling through residential areas near his home in Griffith Park, an island of wilderness and picnic areas in the middle of Los Angeles.

    “P-22’s survival on an island of wilderness in the heart of Los Angeles captivated people around the world and revitalized efforts to protect our diverse native species and ecosystems,” Governor Gavin Newsom said in a statement Saturday.

    Ground was broken this year on the wildlife crossing, which will stretch 200 feet (60.96 meters) over U.S. 101. Construction is expected to be completed by early 2025.

    P-22 usually hunted deer and coyotes, but in November the National Park Service confirmed that the cougar had attacked and killed a Chihuahua mix that was being walked in the narrow streets of the Hollywood Hills.

    The cougar also is suspected of attacking another Chihuahua in the Silver Lake neighborhood this month.

    Beth Pratt with the National Wildlife Federation said she hopes P-22’s life and death will inspire the construction of more wildlife crossings in California and across the nation. The nonprofit was a major advocate for the LA-area bridge.

    “He changed the way we look at LA. And his influencer status extended around the world, as he inspired millions of people to see wildlife as their neighbors,” Pratt said.

    ———

    Associated Press reporter John Antczak contributed.

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  • What Are the Risks of HIV Treatment-Related Weight Gain?

    What Are the Risks of HIV Treatment-Related Weight Gain?

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    Most people with HIV gain weight after they start antiretroviral therapy (ART). In fact, it’s usually a good sign that your ART is working. You might hear your doctor call these early extra pounds a “return to health.” But too much treatment-related weight gain can sometimes lead to future health problems.

    “Three decades ago, when the HIV epidemic was fresh and new, we worried about malnutrition and wasting,” says Onyema Ogbuagu, MBBCh, an infectious disease specialist who treats people with HIV at Yale Medicine. “Now that we’ve done a better job of catching people earlier in the disease and have more effective treatments, we have a different kind of metabolic problem, which is obesity.”

    Tell your doctor if you’re worried about treatment-related weight gain. They’ll go over all the pros and cons of your ART. They’ll also help you find safe ways to lose weight.

    Here are some other topics you might want to go over with your health care team.  

    What Are the Health Risks of Treatment-Related Weight Gain?

    Ogbuagu says older kinds of ART might cause lipodystrophy. That’s when your body shifts how it stores fat. You can end up with the kind of belly fat that’s linked to insulin resistance, diabetes, and heart problems. But those kind of fat changes are a lot less likely to happen with newer drugs.

    But there is evidence that short-term treatment-related weight gain from modern ART can still raise your odds of certain metabolic problems. More research is needed to know all of the long-term effects of treatment. But ART-related weight gain might lead to the following:

    • Type 2 diabetes
    • High cholesterol (also known as hyperlipidemia)
    • Non-alcoholic fatty liver disease

    “The data for diabetes and liver fat is certainly present,” says John Koethe, assistant professor in the division of infectious diseases at Vanderbilt University. But he says there’s conflicting evidence when it comes to cardiovascular disease. Obesity and overweight up the chances anyone will get cardiovascular disease. But he says it’s still not known whether ART-related weight gain raises those odds even higher. We need more research to find out.

    “People with HIV are already at a markedly increased risk of cardiovascular disease,” Koethe says. “The issue there may be that any attributable risk from the weight gain hasn’t really turned up in studies yet.”

    Keep in mind that excess body weight, regardless of which ART you’re on, can raise your odds of certain health conditions. That includes the following:

    • Sleep apnea
    • Cognitive decline
    • High blood pressure
    • Heart disease and stroke

    When Should You Watch for Weight Gain?

    After you start ART, your odds of weight gain are highest within the first 12 to 18 months, Koethe says. In that period of time, studies show about 37% of people will gain 5% of their body weight. Another 17% will add 10% of their body weight.

    Your weight might keep going up for several years after the start of ART, Koethe says, “but at a much slower pace.” 

    Does All Treatment-Related Weight Gain Come With Risks?

    If you’re underweight or normal weight, a few extra pounds can be OK and even healthy. “Weight gain is not always a bad thing,” Ogbuagu says. “For some people, it’s desirable.” He says it might even boost your sense of well-being.

    But in general, Koethe says doctors usually start to worry about future health problems if you gain 5% of your body weight after starting ART. People store that weight in different ways, but he says your odds of certain medical problems go up if you hold fat in the area around your internal organs. 

    “Those folks are at a higher risk of also accumulating fat around the liver, around the heart, and within their skeletal muscles,” Koethe says. “It’s those individuals who are going to be at a higher risk for metabolic diseases like diabetes and other comorbidities down the road.”

    It’s hard to tell where your fat is just by looking at your body. But there are some tests your doctor can do to get a more detailed look. Koethe says that might include the following:

    • Measure around your waist. Your odds of diabetes and heart disease are higher if your waist is greater than 35 inches for women or 40 inches for men.
    • DEXA (or DXA) scan. This is a type of bone density test. But it can also show where your body stores fat and muscle.
    • CT scan. This is a more advanced tool that’ll give your doctor info on the fat in and around your liver, skeletal muscles, heart, or other organs.

    Who Is More Likely to Gain Weight on ART?

    Koethe and his colleagues found that 3 years after the start of ART, about 22% of healthy-weight people became overweight. Among those who were already overweight, he says about one-fifth became obese. But those numbers don’t help experts predict much.

    There’s ongoing research into how much of a role your genes play. Koethe says there’s emerging data that certain drug-metabolizing enzymes might affect weight gain. In the future, that might shine a light on who’s more likely put on extra pounds after the start of ART.

    Should You Change Your ART?

    Talk to your doctor about your treatment. They might want to switch you to a different drug if you’ve gained lots of excess weight. But there are a lot of things to think about it before you make a change.

    If you haven’t started treatment, current pre-ART guidelines include a consideration for weight gain or metabolic problems. Bring it up with your doctor if those are health problems you or other family members have had.

    But right now, Koethe says there’s not enough scientific data to support a change from the standard guidelines. He says that’s because integrase inhibitors, which are linked to weight gain, “are just so much better when it comes to preventing (drug) resistance.”

    The best thing you can do, Koethe says, is to start or continue a healthy diet and exercise routine, especially at the start of ART. And keep your doctor in the loop about your weight gain. They can run routine checks on key health measures, such as:

    • Blood sugar
    • Blood pressure
    • Cholesterol levels

    Your doctor might not choose or change your ART based solely on excess weight concerns. But Ogbuagu says you should still talk to your doctor if it happens. “I think we should take action early, in the first few months or year, so that people don’t continue to gain weight and develop new complications along the way.”

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  • Livers have the potential to function for more than 100 years

    Livers have the potential to function for more than 100 years

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    Key takeaways 

    • Understanding the characteristics of livers that live to 100 could potentially expand the donor pool by using older liver donors more often. 
    • New surgical techniques and advances in immunosuppression lead to better outcomes for patients receiving a liver from an older donor.  
    • Optimizing both donor and recipient factors allow for much greater longevity for certain livers. 

    Newswise — SAN DIEGO: There is a small, but growing, subset of livers that have been transplanted and have a cumulative age of more than 100 years, according to researchers from University of Texas (UT) Southwestern Medical Center, Dallas, and TransMedics, Andover, Massachusetts. They studied these livers to identify characteristics to determine why these organs are so resilient, paving the way for considering the potential expanded use of older liver donors. The research team presented their findings at the Scientific Forum of the American College of Surgeons (ACS) Clinical Congress 2022. 

    The researchers used the United Network for Organ Sharing (UNOS) STARfile to identify livers that had a cumulative age (total initial age at transplant plus post-transplant survival) of at least 100 years. Of 253,406 livers transplanted between 1990-2022, 25 livers met the criteria of being centurion livers—those with a cumulative age over 100 years. 

    “We looked at pre-transplant survival—essentially, the donor’s age—as well as how long the liver went on to survive in the recipient,” said lead study author Yash Kadakia, a medical student at UT Southwestern Medical School. “We stratified out these remarkable livers with over 100-year survival and identified donor factors, recipient factors, and transplant factors involved in creating this unique combination where the liver was able to live to 100 years.” 

    Centurion livers came from older donors 

    For these centurion livers, the average donor age was significantly higher, 84.7 years compared with 38.5 years for non-centurion liver transplants. The researchers noted that for a liver to make it to 100, they expected to find an older average donor age as well as healthier donors. Notably, the donors from the centurion group had lower incidence of diabetes and fewer donor infections. 

    “We previously tended to shy away from using livers from older donors,” said study coauthor Christine S. Hwang, MD, FACS, associate professor of surgery, UT Southwestern Medical Center. “If we can sort out what is special amongst these donors, we could potentially get more available livers to be transplanted and have good outcomes.”  

    There are 11,113 patients on liver transplant waiting list as of September 22, 2022.* As Dr. Hwang noted, using older liver donors more often could potentially expand the liver donor pool. 

    Further study details 

    Centurion liver donors had lower transaminases, which are enzymes that play a key role in the liver. Elevated transaminases can cause problems in liver transplantation. Additionally, the recipients of centurion livers had significantly lower MELD scores (17 for the centurion group, 22 for the non-centurion group). A higher MELD score indicates that a patient is more urgently in need of a transplant.  

    “The donors were optimized, the recipients were optimized, and it takes that unique intersection of factors to result in a really good outcome,” Mr. Kadakia said. 

    The researchers found that no grafts in the centurion group were lost to primary nonfunction or vascular or biliary complications. There was notably no significant difference in rates of rejection at 12 months between the centurion group and the non-centurion group. Further, outcomes for the centurion group had significantly better allograft and patient survival.  

    “The existence of allografts over 100 years old is revealing of the dramatic resilience of the liver to senescent events,” the study authors concluded.  

    “Livers are incredibly resilient organs,” said Mr. Kadakia. “We’re using older donors, we have better surgical techniques, we have advances in immunosuppression, and we have better matching of donor and recipient factors. All these things allow us to have better outcomes.” 

    Study coauthors are Malcolm MacConmara, MBBCh, FACS; Madhukar S. Patel, MD; Jigesh A. Shah, DO; Steven I. Hanish, MD, FACS; and Parsia A. Vagefi, MD, FACS. 

    Citation: Kadakia Y, et al. Centurion Livers — Making It to 100 with A Transplant, Scientific Forum, American College of Surgeons Clinical Congress 2022. 

    ________________________  

    * Data. Organ Procurement & Transplantation Network. Accessed September 23, 2022. Available at: https://optn.transplant.hrsa.gov/data/ (.)  

    # # # 

    About the American College of Surgeons  

    The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 84,000 members and is the largest organization of surgeons in the world. “FACS” designates that a surgeon is a Fellow of the American College of Surgeons. 

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    American College of Surgeons (ACS)

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  • Increased mitochondria and lipid turnover reduces risk for liver cancer

    Increased mitochondria and lipid turnover reduces risk for liver cancer

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    Newswise — Alcohol consumption and hepatitis C viral infection are known risk factors for causing hepatocellular carcinoma, the most common form of liver cancer. Apart from these, obesity-associated nonalcoholic fatty liver disease has emerged as a major contributing factor for hepatocellular carcinoma in Western societies. The mechanisms underlying obesity-induced liver cancer are not well understood.

    A new study published this week in the journal Science Advances by University of Chicago researchers showed that in a mouse model, deletion of the BNIP3 protein resulted in decreased turnover of mitochondria and lipid droplets that led to the development of fatty liver and, ultimately, liver cancer. In human liver cancer, they also showed that loss of BNIP3 expression was linked to increased lipids and worse prognosis.

    “My lab is interested in mitochondria and the turnover of mitochondria in normal physiological settings, but also in cancer. In our studies, we work on a protein called BNIP3 that functions as a mitochondrial cargo receptor,” said Kay Macleod, PhD, senior author of the paper and a professor in the Ben May Department for Cancer Research at the University of Chicago Medicine Comprehensive Cancer Center. “Normally, this protein is significantly upregulated in the liver in response to fasting in mice, where it plays a role in protecting the liver from fat accumulation; however, eliminating this protein caused fatty liver. So we studied this further to understand the underlying mechanisms of how loss of BNIP3 leads to lipid accumulation in the normal liver as well as liver cancer.”

    To understand BNIP3 involvement in the prevention of lipid accumulation and fatty liver condition, liver cancer was induced using chemical carcinogens in two sets of mice, one with BNIP3 intact and the other with BNIP3-deleted. The research team observed that tumors developed earlier and grew faster in BNIP3-deleted mice. Moreover, these tumors were full of fat, whereas tumors in BNIP3-intact mice were smaller and didn’t have lipids in them. When these tumors were followed over time, BNIP3-intact mice also developed lipid accumulation similar to that of BNIP3-deleted mice. More interestingly, BNIP3 had been silenced, suggesting that there is a selection for loss of BNIP3 in liver cancer as the disease progresses.

    These findings were consistent with human liver cancer patient data that reported a better prognosis in patients who had BNIP3 and less lipids in their tumors compared to patients who had a very high expression of genes involved in lipid synthesis. The data again suggests that BNIP3 is acting to suppress tumorigenesis in hepatocellular carcinoma by preventing lipid accumulation. Then the next question is how does BNIP3 regulate lipids?

    When BNIP3 was reintroduced using lentivirus into hepatocellular carcinoma cells that lacked BNIP3, tumor cells stopped accumulating lipids, and they didn’t multiply or grow as fast as the ones that lacked BNIP3. The researchers showed that this was happening due to BNIP3 causing turnover of lipids with mitochondria in a degradative cellular process that they call “mitolipophagy.”

    Fatty liver is a growing health issue in Western societies because of diet. “Eating too much food and eating the wrong kind of food causes extra fat to be stored in the liver. When liver cells (hepatocytes) get overburdened with lipids, they undergo death, which leads to regenerative growth of liver cells. If this process is uninterrupted, it leads to hepatocellular carcinoma,” Macleod said.

    Next, her team wondered how reduced lipid droplet turnover prevents hepatocellular carcinoma. Lipid droplets store a variety of lipids that are used to make cell membranes. If a cell is growing or multiplying, it requires a lot more membrane. BNIP3 will limit the number of phospholipids in the cell thereby limiting the lipids required for new cell generation.

    “BNIP3 is both preventing initiation of tumors and also limiting progression of tumors that are already formed by preventing them from growing faster or becoming more aggressive,” Macleod said.

    This work suggests that for a hepatocellular carcinoma to actually to form, it has to get rid of BNIP3. This implies that if there was a way to somehow prevent BNIP3 from being silenced, this could limit liver tumor growth or prevent fatty liver in the first place.

    “I think the most exciting thing is that BNIP3 does more than just promote the turnover of mitochondria. By promoting the interaction and functionality of the mitochondria, it is actually regulating other organelles in the cell,” Macleod said.

    Much attention has been paid to tumor metabolism and how to target this process in cancers. Most of that tends to focus on amino acids and glucose metabolism but not as much on lipid biology. Understanding more about how lipid metabolism is deregulated in cancer has not been as heavily researched. The researchers’ future work focuses on understanding how BNIP3 is regulated in disease conditions as well as with age. Meanwhile, they are also interested in a number of other genes that play important roles in response to nutrient stress.

    The study, “Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3- 3 dependent manner” was supported by NIH R01 849 CA200310 and NIH T32 CA009594. Additional authors include Damian Berardi, Althea Bock-Hughes, Alexander Terry, Lauren Drake and Grazyna Bozek from the University of Chicago.

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    University of Chicago Medical Center

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  • Liver Cancer: Excessive Alcohol Use and Other Risks

    Liver Cancer: Excessive Alcohol Use and Other Risks

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    Newswise — New Brunswick, N.J., October 1, 2022 – The liver is one of the most important organs in the body. It removes toxins from the blood and regulates the levels of chemicals. It excretes a product called bile which helps you digest fat. It makes clotting factors and stores sugar that the body uses for energy. Many may associate poor liver health with increased alcohol consumption but does that mean that drinking alcohol causes liver cancer? Mariam F. Eskander, MD, MPH, surgical oncologist at Rutgers Cancer Institute of New Jersey, the state’s leading cancer center only National Cancer Institute (NCI)-designated Comprehensive Cancer Center, together with RWJBarnabas Health, and assistant professor of surgery at Rutgers Robert Wood Johnson Medical School whose clinical expertise includes liver tumors, shares more information on this topic.

    Q: What is the relationship between excessive alcohol use and liver cancer?

    Heavy alcohol use is toxic to the liver. Alcohol abuse can cause irreversible damage to the liver called cirrhosis, and cirrhosis is the biggest risk factor for the development of hepatocellular carcinoma, the most common type of liver cancer. Other risk factors are chronic hepatitis B or C and nonalcoholic fatty liver disease, which can also lead to cirrhosis. Smoking is another risk factor.

    Q: What are ways to lower liver cancer risk?

    Take care of your liver! This means avoiding excessive alcohol intake, maintaining a healthy weight, and not smoking.

    Q: Are there any early signs or symptoms of liver cancer?

    Unfortunately, there are not any early signs of liver cancer. However, patients may present with abdominal pain, weight loss, nausea or vomiting, and yellowing of the skin or eyes.

    Q: Is liver cancer hereditary?

    Generally, no. There are some genetic conditions that increase the risk of developing liver cancer but they are not common. These include hereditary hemochromatosis and alpha-1 antitrypsin deficiency.

    Q: Should people who have liver cancer abstain from drinking alcoholic beverages?

    Yes, people who have liver cancer should avoid drinking alcohol. It can worsen liver function and limit treatment options. It can also increase the risk of developing another type of cancer.

    Q: What should I do if I think I’m at risk for liver cancer?

    Talk to your primary care physician about your specific risk factors and actions you can take to lower your risk. People with cirrhosis should also see a liver specialist to improve their liver health and get regular ultrasound screenings for liver cancer.

    At Rutgers Cancer Institute, the Liver Cancer and Bile Duct Cancer Program is the state’s only multidisciplinary health care group focused on liver and bile duct tumors. Learn more about our Liver Cancer and Bile Duct Cancer Program.

     

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    Rutgers Cancer Institute of New Jersey

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