The future of diagnosing and monitoring NAFLD/NASH could be noninvasive – Pharmaceutical Technology
The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) continues to increase, compounded by risk factors such as advanced age, obesity, ethnicity, and type 2 diabetes mellitus (T2DM). As NAFLD progresses to NASH, the same factors also contribute to liver fibrogenesis (abnormal accumulation of fibrous tissue). Constant liver damage results in progressive scarring (fibrosis), which disrupts the structural integrity of the liver through fibrosis bands, parenchyma nodules, and blood vessel abnormalities, leading to cirrhosis. Hence, liver fibrosis is a key criterion that represents the severity of liver illnesses and is an important factor that helps physicians forecast the progression of liver disorders towards cirrhosis.
Although liver biopsies are currently considered to be the gold standard for the diagnosis and histological assessment of NAFLD/NASH, they are not without limitations (Li et al., 2022; Zeng et al., 2022). In addition to being a costly and invasive procedure, the estimated number of patients with NASH vastly outnumbers the number of specialists with the proper skills and expertise to perform and interpret a liver biopsy. Additionally, liver biopsies are prone to sampling errors, as fibrosis is not uniform throughout the liver, making it difficult to distinguish between the stages of fibrosis. As such, there has been much interest in developing non-invasive tests (NITs) to detect markers of fibrosis. These NITs are usually categorised based on the test’s modality, such as imaging or serum blood tests, or components like direct markers versus indirect markers of fibrosis.
Serum biomarkers identified via multi-biomarker panel blood tests and non-invasive imaging tests such as transient elastography (VCTE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) can be used to identify patients with liver steatosis, determine the stage of fibrosis, and diagnose NAFLD/NASH. While non-invasive imaging and serum blood tests are cost-effective, accessible, and have high reproducibility compared to a liver biopsy, they also have limitations. Table 1 highlights some of the key limitations of current NITs.
Despite these limitations, the American Association for the Study of Liver Diseases (AASLD) recently published its 2023 NAFLD Practice Guidance to suggest the use of vibration controlled transient elastography (VCTE), a patented technology used by Echosens’s FibroScan for detecting and diagnosing NAFLD in high-risk individuals, including those with type 2 diabetes. FibroScan is a non-invasive device that assesses the ‘hardness’, or stiffness, of the liver via transient elastography, an ultrasound-based technology.
However, with the possibility of the first set of approvals for NASH therapies coming soon, data on the performance of NITs being used in current Phase III clinical trials could help address their limitations for diagnosis and treatment monitoring in NASH. In addition to making the diagnosis process more economic and accessible, the use of NITs in lieu of a liver biopsy could help shape the future treatment paradigm of NAFLD/NASH.
Li, G., et al. (2022) ‘Non-invasive tests of non-alcoholic fatty liver disease’, Chinese Medical Journal, 135(5), pp. 532–546. Available at: https://journals.lww.com/cmj/Fulltext/2022/03050/Non_invasive_tests_of_non_
alcoholic_fatty_liver.7.aspx (Accessed: 22 February 2023).
Patel, K. and Sebastiani, G. (2020) ‘Limitations of non-invasive tests for assessment of liver fibrosis’, JHEP Reports, 2(2). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047178/ (Accessed: 22 February 2023).
Zeng, Y., et al. (2022) ‘Advance of serum biomarkers and combined diagnostic panels in nonalcoholic fatty liver disease’, Disease Markers. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259243/ (Accessed: 22 February 2023).
What made Beethoven sick? DNA from his hair offers clues
Nearly 200 years after Ludwig van Beethoven’s death, researchers pulled DNA from strands of his hair, searching for clues about the health problems and hearing loss that plagued him.
They weren’t able to crack the case of the German composer’s deafness or severe stomach ailments. But they did find a genetic risk for liver disease, plus a liver-damaging hepatitis B infection in the last months of his life.
These factors, along with his chronic drinking, were probably enough to cause the liver failure that is widely believed to have killed him, according to a study published Wednesday in the journal Current Biology.
This Sunday marks the 196th anniversary of Beethoven’s death in Vienna on March 26, 1827, at the age of 56. The composer himself wrote that he wanted doctors to study his health problems after he died.
“With Beethoven in particular, it is the case that illnesses sometimes very much limited his creative work,” said study author Axel Schmidt, a geneticist at University Hospital Bonn in Germany. “And for physicians, it has always been a mystery what was really behind it.”
Since his death, scientists have long tried to piece together Beethoven’s medical history and have offered a variety of possible explanations for his many maladies.
Now, with advances in ancient DNA technology, researchers have been able to pull genetic clues from locks of Beethoven’s hair that had been snipped off and preserved as keepsakes. They focused on five locks that are “almost certainly authentic,” coming from the same European male, according to the study.
They also looked at three other historical locks, but weren’t able to confirm those were actually Beethoven’s. Previous tests on one of those locks suggested Beethoven had lead poisoning, but researchers concluded that sample was actually from a woman.
After cleaning Beethoven’s hair one strand at a time, scientists dissolved the pieces into a solution and fished out chunks of DNA, said study author Tristan James Alexander Begg, a biological anthropologist at the University of Cambridge.
Getting genes out was a challenge, since DNA in hair gets chopped up into tiny fragments, explained author Johannes Krause, a paleogeneticist at Germany’s Max Planck Institute for Evolutionary Anthropology.
But eventually, after using up almost 3 metres of Beethoven’s hair, they were able to piece together a genome that they could “quiz” for signs of genetic disease, Dr. Krause said.
While researchers didn’t find any clear genetic signs of what caused Beethoven’s gastrointestinal issues, they found that celiac disease and lactose intolerance were unlikely causes. In the future, the genome may offer more clues as we learn more about how genes influence health, Mr. Begg said.
The research also led to a surprising discovery: When they tested DNA from living members of the extended Beethoven family, scientists found a discrepancy in the Y chromosomes that get passed down on the father’s side. The Y chromosomes from the five men matched each other – but they didn’t match the composer’s.
This suggests there was an “extra-pair paternity event” somewhere in the generations before Beethoven was born, Mr. Begg said. In other words, a child born from an extramarital relationship in the composer’s family tree.
The key question of what caused Beethoven’s hearing loss is still unanswered, said Ohio State University’s Dr. Avraham Z. Cooper, who was not involved in the study. And it may be a difficult one to figure out, because genetics can only show us half of the “nature and nurture” equation that makes up our health.
But he added that the mystery is part of what makes Beethoven so captivating: “I think the fact that we can’t know is okay,” Dr. Cooper said.
Around 410 London, Ont. students remain suspended for lacking vaccine records
Around 410 London and Middlesex area students remain suspended from school as of Wednesday evening for lacking submitted immunization records with the Middlesex-London Health Unit.
MLHU officials say that while over 1,100 students were set to be suspended Wednesday, that number had dropped to 675 by 11 a.m. and then again to 410 by 5 p.m. as parents submitted proper documentation.
The local health unit resumed suspending elementary or high school students in January for not having up-to-date immunization records.
Because there are so many students lacking documentation with the health unit, the suspensions are being done in seven different cohorts between January and the end of May. The suspensions this week are for the fourth cohort.
Dr. Alex Summers, the medical officer of health for Middlesex-London, says it is not a mandatory vaccination issue but instead a mandatory reporting issue.
“We know that there is probably a number of students out there that have received the vaccines, but we just don’t have their records,” said Summers.
Under the Ontario Immunization of Student Pupils Act, Grade 1-12 students are required to have up-to-date immunization reporting for nine preventable diseases. If a student’s vaccination or a valid exemption is not recorded, the local health has the authority to issue school suspensions.
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Students must be immunized against diphtheria, tetanus, polio, measles, mumps, rubella, meningococcal disease and whooping cough. Kids born in 2010 or later are also required to have the chickenpox shot.
Once a child is vaccinated, families are responsible for submitting the updated records to the health unit or submitting an exemption.
The health unit began the process of getting immunization records updated again a little under a year ago, sending out 42,000 letters last school year to families with missing records.
The first two cohorts in January and February had a combined 2,300 suspensions from 7,600 notices issued a month before the suspensions.
“Rapidly, many of those students come off the suspension list because that due date really helps people move forward with submitting records or getting vaccinations done,” said Summers.
None of the students suspended in the first two cohorts remain away from school.
The third cohort, which had its suspensions begin on March 1, has had the vast majority of students return to school, with less than 60 continuing to be suspended from 3,300 notices.
A spokesperson for the Thames Valley District School Board says the board supports all students who are not able to learn in-person, no matter the reason.
“Educators post work in the digital classrooms and families can reach out to the school/educator directly for independent learning activities,” said the board in a statement in Global News.
The MLHU has run 28 special clinics since the start of 2023 to help students and parents catch up on vaccinations that may have been missed during the COVID-19 pandemic. Over 2,000 people have received over 4,000 vaccines during the special clinics.
Summers says catch-up clinics will continue to run into April to give families every opportunity to get caught up on vaccines. And while the issue is considered a documentation and not a vaccination issue, Summers says vaccines are essential to a healthy life.
“Because of the vaccines we have available to us, we have a much significantly higher quality of life than we used to a 100 years ago,” said Summers.
“Without high vaccination coverage in our region, we will see outbreaks locally.”
‘Worsening spread’ of deadly fungal infection raising alarm in U.S.
Cases of a drug-resistant infection caused by the fungus Candida auris are on the rise in the United States, according to new data from the Centers for Disease Control and Prevention (CDC). The fungal infection has proved deadly, especially for those with compromised immune systems, and has demonstrated an ability to spread easily in health-care settings.
The CDC data was published Monday in the Annals of Internal Medicine, amid an outbreak of fungal infections in long-term care facilities in Mississippi. The U.S. health agency found that cases of C. auris increased 95 per cent from 2020 to 2021 following a 44 per cent increase the year prior.
Preliminary figures estimate that there were 2,377 active C. auris infections across the U.S. in 2022, with 5,754 “colonization” cases. A colonization case denotes when a person has evidence of the fungus in their body without signs of an active infection.
C. auris, a type of yeast that can infect the bloodstream, is resistant to multiple anti-fungal drugs and is estimated to kill about 40 per cent of people who become infected, according to Health Canada. Even when patients survive, they can remain “colonized” with the fungus for years after treatment, the CDC says, and potentially pass it along unsuspectingly.
These fungal infections are of most concern to people who have been hospitalized for long periods of time, are at high risk of infection, or have medical implants. The organism often causes no symptoms in healthy people.
C. auris was first detected in the U.S. in 2016, though case numbers remained low until the “dramatic increase in 2021,” the CDC report reads. The fungus was first discovered in 2009 in Japan and has since caused outbreaks in numerous countries around the world.
Rising cases of C. auris infections, “especially in the most recent years, are really concerning to us,” said the study’s lead author, Dr. Meghan Lyman, chief medical officer in the CDC’s Mycotic Diseases Branch. “We’ve seen increases not just in areas of ongoing transmission, but also in new areas.”
“There’s still a lot to learn about colonization patterns,” Lyman said. “While (medicine) may treat the infection, we don’t have evidence that it completely eliminates C. auris from their body.”
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Between 2012 and 2021, there were 31 cases of C. auris found in hospitalized patients in Canada, according to data from the National Microbiology Laboratory and Canadian Nosocomial Infection Surveillance Program.
The CDC’s warnings come as Mississippi battles an outbreak of the fungus.
At least 12 people in the state have been infected with the fungus with four “potentially associated deaths,” said Tammy Yates, spokesperson for the Mississippi State Department of Health. Both those numbers doubled since an earlier update on the outbreak in January. The first cases were noticed in the state last year in November.
Transmission of the infections occurred in two long-term care homes, with Yates noting that “multi-drug resistant organisms such as C. auris have become more prevalent” in such facilities and among “highest risk individuals.”
The World Health Organization ranked C. auris as one of the worst fungal threats facing humanity today, given its high mortality rate and resistance to treatment. Recent research suggests that serious fungal infections as a whole affect 300 million people worldwide and more than 1.5 million die from them each year.
Dr. Waleed Javaid, director of infection prevention and control at Mount Sinai Downtown in New York, said that the new CDC data on C. auris is “worrisome.”
“But we don’t want people who watched The Last of Us to think we’re all going to die,” Javaid said. “This is an infection that occurs in extremely ill individuals who are usually sick with a lot of other issues.”
Global News has reached out to Health Canada for further comment on the current status of C. auris infections in the country.
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