steatohepatitis nash – Rogalevich http://rogalevich.org/ Sat, 26 Mar 2022 12:36:46 +0000 en-US hourly 1 https://wordpress.org/?v=5.9.3 https://rogalevich.org/wp-content/uploads/2021/10/icon-120x120.png steatohepatitis nash – Rogalevich http://rogalevich.org/ 32 32 Fatty liver disease is common in young people living with HIV https://rogalevich.org/fatty-liver-disease-is-common-in-young-people-living-with-hiv/ Mon, 31 Jan 2022 19:33:50 +0000 https://rogalevich.org/fatty-liver-disease-is-common-in-young-people-living-with-hiv/ About a third of young people living with HIV may have non-alcoholic fatty liver disease (NAFLD), according to the results of a study published in AIDS. The analysis revealed that fatty liver disease was only partially explained by overweight and metabolic syndrome. Resulting from fatty accumulation in the liver, NAFLD and its most severe form, […]]]>

About a third of young people living with HIV may have non-alcoholic fatty liver disease (NAFLD), according to the results of a study published in AIDS. The analysis revealed that fatty liver disease was only partially explained by overweight and metabolic syndrome.

Resulting from fatty accumulation in the liver, NAFLD and its most severe form, non-alcoholic steatohepatitis (NASH), are responsible for an increasing proportion of advanced liver disease worldwide. As a result of inflammation, NAFLD can lead to fibrosis, cirrhosis, and even liver cancer. Fatty liver disease is often accompanied by abdominal obesity, hypertension, and abnormal blood sugar and fat levels, collectively known as metabolic syndrome. In the absence of effective approved medical therapies, the management of NAFLD depends on lifestyle changes, such as weight loss and exercise.

Although fatty liver disease is known to be common in people living with HIV, data on younger people who acquired perinatal HIV, that is, acquired HIV during gestation or during time of birth, are lacking.

Talia Sainz, MD, PhD, of the Health Research Institute of La Paz Hospital in Madrid, and her colleagues conducted a prospective study of 38 children, adolescents and young people who acquired HIV during the perinatal period and 38 young HIV-negative matched for age and sex. More than half (59%) were young women and the median age was 19 years old. All people living with HIV were receiving antiretroviral therapy at the start of the study; 87% had viral suppression. Noninvasive imaging was used to determine the presence of NAFLD or fibrosis, and four different scores were used to predict NAFLD.

The researchers found that 11 HIV-positive young people (29%) had been diagnosed with NAFLD by imaging, compared to only three HIV-negative people (8%). Clinical parameters and analytical scores did not accurately identify participants at risk for NAFLD. People with NAFLD had a significantly higher BMI and were somewhat more likely to be overweight, although this was not statistically significant. HIV-related parameters, such as viral load and CD4 cell count, generally did not differ significantly in people with and without fatty liver disease, except that the CD4/CD8 T-cell ratio was lower in those with and without fatty liver disease. HIV-positive people diagnosed with NAFLD.

“The prevalence of NAFLD was high” in people with HIV acquired during the perinatal period and was “only partially explained by overweight and metabolic syndrome defining factors,” the researchers concluded.

“Noninvasive imaging techniques offer an opportunity to treat nonalcoholic fatty liver disease in a population in which validated scores for adults have not been tested,” they wrote. [L]Ultrasound evaluation of the liver should be considered for NAFLD screening in [people with perinatally acquired HIV] in routine clinical practice.

Click here to read the summary of the study in AIDS.

Click here for more information on fatty liver disease.


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Lifestyle changes improve liver health in children with NAFLD https://rogalevich.org/lifestyle-changes-improve-liver-health-in-children-with-nafld/ Fri, 28 Jan 2022 14:31:49 +0000 https://rogalevich.org/lifestyle-changes-improve-liver-health-in-children-with-nafld/ An intensive lifestyle management program for children and adolescents with non-alcoholic fatty liver disease (NAFLD) significantly reduced liver fibrosis and fat accumulation, according to study results published in Clinical Gastroenterology and Hepatology . Resulting from fatty accumulation in the liver, NAFLD and its most severe form, non-alcoholic steatohepatitis (NASH), are responsible for an increasing proportion […]]]>

An intensive lifestyle management program for children and adolescents with non-alcoholic fatty liver disease (NAFLD) significantly reduced liver fibrosis and fat accumulation, according to study results published in Clinical Gastroenterology and Hepatology .

Resulting from fatty accumulation in the liver, NAFLD and its most severe form, non-alcoholic steatohepatitis (NASH), are responsible for an increasing proportion of advanced liver disease worldwide. As a result of inflammation, NAFLD can lead to fibrosis, cirrhosis, and even liver cancer. In the absence of effective approved medical therapies, management depends on lifestyle changes, such as weight loss and exercise. But research on lifestyle interventions for children with fatty liver disease has been limited.

Sander Lefere, MD, PhD, of the Ghent University Liver Research Center in Belgium, and colleagues studied the impact of lifestyle management on children and adolescents with severe obesity. The intensive lifestyle intervention, conducted in a multidisciplinary residential setting, included calorie reduction, exercise, healthy living counseling and psychosocial support. Liver imaging was performed at baseline and at six and 12 months into the study to determine the presence of hepatic fat and fibrosis. The results of the study have already been presented at the AASLD liver meeting.

A total of 204 participants with a median age of 14 years were included in the study. Using ultrasound, NAFLD was identified in 71% of participants; 20% of them had a severe case. More than two-thirds had a high controlled attenuation parameter (CAP) score indicating hepatic steatosis. The CAP score measures the intensity of sound waves as they pass through fatty tissue compared to normal liver tissue. A third had moderate fibrosis (stage F2) and 10% had a FibroScan value indicating more severe liver scarring.

After six months of the program, 167 participants experienced a median weight loss of 16%. Fibrosis improved in 75% of participants, and fibrosis resolution was predicted by the degree of scarring and liver fat at baseline. A total of 79 participants reached the one-year milestone, and the improvement continued. All participants who had fibrosis at baseline experienced fibrosis regression of at least one stage.

“NAFLD and associated fibrosis are highly prevalent in children and adolescents with severe obesity,” the researchers wrote. “An intensive multidisciplinary lifestyle management program that results in significant weight loss not only improves fatty liver disease, but fibrosis as well.”

Click here to read the study abstract in Clinical Gastroenterology and Hepatology.

Click here for more information on fatty liver disease.


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Underlying liver disease does not affect HCC survival after immune checkpoint inhibition https://rogalevich.org/underlying-liver-disease-does-not-affect-hcc-survival-after-immune-checkpoint-inhibition/ Tue, 25 Jan 2022 13:05:35 +0000 https://rogalevich.org/underlying-liver-disease-does-not-affect-hcc-survival-after-immune-checkpoint-inhibition/ January 25, 2022 2 minute read Source/Disclosures Published by: Source: WuYL, et al. Abstract 396. Presented at: ASCO Gastrointestinal Cancers Symposium; January 20-22, 2022; San Francisco. Disclosures: Wu does not report any relevant financial information. Please see the summary for all relevant financial disclosures from other researchers. ADD A SUBJECT TO EMAIL ALERTS Receive an […]]]>

January 25, 2022

2 minute read

Source:

WuYL, et al. Abstract 396. Presented at: ASCO Gastrointestinal Cancers Symposium; January 20-22, 2022; San Francisco.

Disclosures: Wu does not report any relevant financial information. Please see the summary for all relevant financial disclosures from other researchers.


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According to study results presented at the ASCO Symposium on Gastrointestinal Cancers, the benefit of immune checkpoint inhibitor therapy for hepatocellular carcinoma did not vary by underlying liver disease. underlying.

Patients with HCC of viral origin achieved numerically longer OS than those with disease of nonviral origin; however, the difference did not reach statistical significance.

Main results of the study.
Data derived from Wu YL, et al. Abstract 396. Presented at: ASCO Gastrointestinal Cancers Symposium; January 20-22, 2022; San Francisco.

“Further studies with increased granularity are needed to more clearly identify patients with unresectable HCC who are more likely to have better outcomes with immunotherapy,” the researcher said. Linda Wu, MD, fellow in hematology and medical oncology at Mount Sinai Hospital, Healio told.

Immune checkpoint inhibitors, alone or in combination with bevacizumab (Avastin, Genentech), have become standard treatment for patients with unresectable HCC. Although this class of agent has improved HCC outcomes, only a small percentage of patients respond to it.

“[This highlights] the need to identify biomarkers to improve patient selection,” Wu said. “Emerging evidence suggests that patients with nonviral causes of HCC, particularly nonalcoholic steatohepatitis (NASH), may not derive the same benefit of immunotherapy as those with viral causes.We hoped to use real-world data to assess whether patients with viral HCC had better survival outcomes when treated with immunotherapy compared to patients with HCC not viral.

Wu and colleagues performed a retrospective chart review of 349 patients (median age, 63 years; 84% male) with unresectable HCC treated with immune checkpoint inhibitors between January 2017 and June 2021 at Mount Sinai Health System. The researchers characterized the majority (86%) of the patients as cirrhotic.

Most patients (70%) had HCC of viral etiology, with two-thirds (67.5%) of these cases due to hepatitis C infection. Thirty percent of patients had non-viral causes of HCC, with the most common causes being NASH (47%) and alcohol (39%).

The majority of patients had Child-Pugh class A liver disease (66%) and an ECOG performance status of 0 (71%) at the time of immune checkpoint inhibitor initiation.

Most patients (79%) received immune checkpoint inhibitors as first-line treatment, and the majority (87%) received nivolumab (Opdivo, Bristol Myers Squibb).

The difference in OS between patients with viral etiologies and non-viral etiologies of HCC served as the primary outcome. These groups appeared balanced with respect to age, gender, cirrhosis, ECOG performance status, line of treatment, and type of immune checkpoint inhibitor received.

After a median follow-up of 10.5 months (range: 1.4-62.4), researchers reported longer median OS in patients with viral HCC (19.3 months; 95% CI, 14. 2-26.6) than in patients with nonviral HCC (11.4 months; 95% CI, 9.3-17.7). However, the difference – after adjusting for Child-Pugh class and disease stage – did not reach statistical significance (HR = 0.81; 95% CI, 0.58-1.12).

“The lack of statistical significance was somewhat surprising, as several studies have now shown this trend of improved survival in patients with viral HCC treated with immunotherapy,” Wu told Healio. “However, the study may have been underpowered.”

The result underscores the need to better define the subgroups of patients most likely to benefit from immunotherapy, Wu added.

“Although immunotherapy has revolutionized the treatment of advanced unresectable HCC, only about a third of patients respond, based on the IMbrave150 trial,” Wu said. to immunotherapy are important for optimizing patient selection, and we hope that matching patients with optimal therapy would also improve patient outcomes.”

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Non-alcoholic fatty liver disease | Running can keep the liver healthy https://rogalevich.org/non-alcoholic-fatty-liver-disease-running-can-keep-the-liver-healthy/ Thu, 20 Jan 2022 14:02:44 +0000 https://rogalevich.org/non-alcoholic-fatty-liver-disease-running-can-keep-the-liver-healthy/ Running and weight training are two activities that can prevent a condition known as non-alcoholic fatty liver disease (NAFLD), new search shows. This may be because exercise helps reduce inflammation in your body and build lean muscle mass which can help replace fat, two factors that cause NAFLD. Running benefits your heart, brain and muscles, […]]]>


  • Running and weight training are two activities that can prevent a condition known as non-alcoholic fatty liver disease (NAFLD), new search shows.
  • This may be because exercise helps reduce inflammation in your body and build lean muscle mass which can help replace fat, two factors that cause NAFLD.

    Running benefits your heart, brain and muscles, and new research suggests your liver may see the benefits too.

    A condition known as metabolic liver disease or non-alcoholic fatty liver disease (NAFLD) involves fatty deposits in the liver that increase over time and negatively affect your mitochondria (which play a role in energy transformation that we get from food into energy that our cells can use). It can impact how you metabolize carbohydrates, fats, and proteins, and can lead to organ damage if left untreated.

    A recent study in the review Molecular metabolism suggests that exercise may alter mitochondrial function enough to reduce the development of fatty liver deposits. The researchers fed mice a high-calorie diet to promote the development of liver fat, then had some of them train on a treadmill for six weeks. At the end of this period, those who had run showed more regulated liver enzymes and better mitochondrial activity.

    Previous studies in people have shown the same link between better liver function and regular exercise. For example, a Randomized clinical trial 2016 on those with NAFLD showed that vigorous and moderate exercise improved markers of liver health. And comment in 2018 in Gene expression noted that exercise increases fatty acid oxidation and prevents mitochondrial damage in the liver.

    Although the prevention of NAFLD may seem less important than other health risks like cardiovascular disease, cancer or dementia, the prevalence rate of the disease indicates that it is a health problem major and could get worse. When the disease progresses to a more serious form, it is called non-alcoholic steatohepatitis (NASH) and causes swelling and damage to the liver.

    According to American Liver Association, about 1 in 4 people have NASH and most are between 40 and 60 years old. Up to a quarter of those affected develop cirrhosis, a delayed scarring of the liver that may require a transplant.

    A study 2018 estimates that NAFLD will increase by 21% between 2015 and 2030, while NASH is expected to increase by 63% over the same period. These researchers predict that deaths from these liver diseases will increase by 178% by 2030.



    “The good news is that lifestyle changes can make a big difference, both in preventing NAFLD, as well as controlling or even reversing the condition if you have it,” Jeff McIntyre, director of the NASH program for the Global Liver Institute, said The runner’s world.

    He said that in addition to regular activity like running, other lifestyle strategies include avoiding foods with added sugar – a potentially major cause of liver inflammation, he said. – and incorporate strength training into your routine, as lean muscle mass can help replace fat.

    “There are no approved drugs for NASH or NAFLD yet, so the primary prevention and treatment strategy is exercise and nutrition,” he said. “Plus, you’ll benefit other aspects of your body at the same time, like your cardiovascular system and your cognitive health. So movement really is medicine.

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    Development of fatty liver disease as part of a healthy diet https://rogalevich.org/development-of-fatty-liver-disease-as-part-of-a-healthy-diet/ Tue, 18 Jan 2022 19:19:31 +0000 https://rogalevich.org/development-of-fatty-liver-disease-as-part-of-a-healthy-diet/ A new study identifies two genes, previously reported to be involved in cancer, as regulators of the metabolic state of the liver. Alterations in these genes influence the likelihood of developing fatty liver disease. The worldwide obesity epidemic has increased the risk of fat accumulation in the liver, a prelude to liver inflammation and liver […]]]>

    A new study identifies two genes, previously reported to be involved in cancer, as regulators of the metabolic state of the liver. Alterations in these genes influence the likelihood of developing fatty liver disease.

    The worldwide obesity epidemic has increased the risk of fat accumulation in the liver, a prelude to liver inflammation and liver disease. Yet a still intriguing paradox is the development of fatty liver disease in lean, normal-weight individuals and in individuals following a healthy diet. Scientists know that two genes, RNF43 and ZNRF3, are mutated in patients with liver cancer. However, their role in the development of liver cancer was until now unknown. Researchers at the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, now describe that a loss or mutation of these genes causes lipid accumulation and inflammation in the liver in non-obese mice fed diet. These genetic alterations not only increase fat accumulation but also the number of proliferating liver cells (hepatocytes). In human patients, these alterations also increase the risk of developing NASH and fatty liver disease and reduce the patient’s survival time. These discoveries could facilitate the discovery of people at risk and could promote new therapeutic interventions and better management of the disease.

    The liver is our central metabolic organ, which is vital for detoxification and digestion. Chronic liver diseases, such as cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH, inflamed liver), as well as liver cancer, are on the rise worldwide, with a combined mortality of two million people who die each year. It is therefore more important than ever to understand their causes and the underlying molecular mechanisms of liver disease in order to prevent, manage and treat these growing patient subgroups. Previous cancer genomics studies have identified RNF43 and ZNRF3 as mutated genes in colon and liver cancer patients. However, their role in liver disease has not been explored. Meritxell Huch’s research laboratory at MPI-CBG, in collaboration with colleagues from the Gurdon Institute (Cambridge, UK) and the University of Cambridge, has now investigated the mechanisms by which alterations in these two genes can affect the emergence of liver diseases. . Their study is published in the journal Communication Nature.

    To pursue this goal, the researchers worked with mice as an animal model, data from human individuals, human tissues and cultures of liver organoids, which are 3D cellular microstructures consisting of liver-like hepatocytes in a box. Germán Belenguer, first author of the study and postdoctoral researcher in Meritxell Huch’s group, explains: “With the organoid, we were able to grow hepatocytes mutated only in these genes, and we saw that the loss of these ci activates a signal that regulates lipid metabolism. As a result, fat metabolism is no longer under control and lipids accumulate in the liver, which in turn leads to fatty liver disease. Another consequence of the activated signal is that the hepatocytes multiply uncontrollably. The two mechanisms combined facilitate progression to fatty liver disease and cancer.” The scientists then compared the results of the experiments with patient data in a publicly available dataset from the International Cancer Genome Consortium. They assessed the survival prognosis when both genes are mutated in liver cancer patients and found that patients with these mutated genes had fatty liver disease and had a worse prognosis than liver cancer patients whose the two genes had not mutated.

    “Our results can help identify individuals who carry an RNF43/ZNRF3 mutation and therefore are at risk of developing fatty liver disease or liver cancer,” says Meritxell Huch. She continues, “With the alarming increase in fat and sugar consumption around the world, recognizing individuals already predisposed because they carry these genetic mutations could be important for therapeutic intervention and disease management, especially particular at very early stages or even before the We will need more studies to further characterize the roles of the two genes in human fatty liver disease, NASH and human liver cancer and to identify therapeutics that may help patients who are already inherently predisposed to developing the disease.

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    Fatty Liver Disease Symptoms: Five Signs You Might Be Missing https://rogalevich.org/fatty-liver-disease-symptoms-five-signs-you-might-be-missing/ Sat, 15 Jan 2022 11:21:38 +0000 https://rogalevich.org/fatty-liver-disease-symptoms-five-signs-you-might-be-missing/ Non-alcoholic fatty liver disease, or NAFLD, is “a term for a range of conditions caused by an accumulation of fat in the liver”, states the NHS. Cases of NAFLD, like other conditions, are increasing worldwide, especially in Western countries. There are five key signs and symptoms to look out for that could indicate the presence […]]]>

    Non-alcoholic fatty liver disease, or NAFLD, is “a term for a range of conditions caused by an accumulation of fat in the liver”, states the NHS. Cases of NAFLD, like other conditions, are increasing worldwide, especially in Western countries. There are five key signs and symptoms to look out for that could indicate the presence of a condition known as nonalcoholic steatohepatitis, or NASH, for short. The earlier these symptoms are spotted, the sooner they can be treated.

    Symptoms of NASH, a condition that can develop alongside NAFLD, include:
    • Jaundice (yellowing of the eyes and skin)
    • Enlarged blood vessels just below the surface of the skin
    • Enlarged spleen
    • Abdominal swelling
    • Red palm trees

    In addition to NAFLD, these symptoms can also be a sign of advanced scarring; also known as cirrhosis.

    READ MORE: Symptoms of the Omicron variant The sign appearing while eating – “it may come as a surprise”

    In the UK, NAFLD is estimated to affect millions of people.

    It is estimated that a third of the population shows early symptoms of the disease.

    The NHS says “early-stage NAFLD usually causes no harm”.

    However, just like other conditions, if the condition is allowed to get worse, it can lead to serious health issues.

    DO NOT MISS

    Although there is no specific medicine to treat the disease, if it is a more advanced medicine, it can be used to manage the side effects of the disease.

    If there is severe cirrhosis of your liver and the organ stops working properly, a transplant may be recommended.

    For some this may require an entire transplant, while for others only part of the liver may need to be removed.

    Fortunately, since the liver can grow back, it should return to its normal size after the operation.

    There are a number of factors that will increase the risk of developing NAFLD.

    Weight will be a major factor, as will whether or not a person has a habit of smoking.

    People over 50 are also at higher risk, as are those with high cholesterol, high blood pressure and type 2 diabetes.

    People with metabolic syndrome, a condition that combines diabetes, high blood pressure and obesity, are also at higher risk of developing NAFLD.

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    Air pollution linked to fatty liver disease, lung cancer https://rogalevich.org/air-pollution-linked-to-fatty-liver-disease-lung-cancer/ Thu, 13 Jan 2022 00:22:30 +0000 https://rogalevich.org/air-pollution-linked-to-fatty-liver-disease-lung-cancer/ Two recent studies have identified links between ambient air pollution and disease, highlighting the need for populations at risk to be aware of the air quality in the areas where they live and to minimize their exposure to it. pollution to the extent possible. The incidence of metabolism-associated fatty liver disease (MAFLD), formerly known as […]]]>
    Air pollution linked to fatty liver disease, lung cancer

    Two recent studies have identified links between ambient air pollution and disease, highlighting the need for populations at risk to be aware of the air quality in the areas where they live and to minimize their exposure to it. pollution to the extent possible.

    The incidence of metabolism-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has increased steadily since the 1980s, currently affecting a quarter of the world’s population and the majority of patients with the disease. adult fatty liver disease. Diabetes. With the potential to progress to end-stage liver diseases such as cirrhosis and liver cancer, liver transplantation, and liver-related deaths, MAFLD reached 40% of the population in Asia between 2012 and 2017.

    Animal studies have shown that breathing air pollutants can increase the risk of MAFLD; for example, exposure to fine particles can trigger a non-alcoholic steatohepatitis (NASH) -like phenotype, alter hepatic glucose metabolism, and promote hepatic fibrogenesis. But with limited epidemiological evidence for this association, researchers led by Sichuan UniversityDr Xing Zhao set out to improve their understanding of the effects of air pollution on human health.

    Investigators conducted an epidemiological study on the potential role of ambient air pollution in the risk of MAFLD in approximately 90,000 adults in China based on the China Multi-Ethnic Cohort (CMEC) baseline survey. , a prospective cohort that recruited nearly 100,000 participants in southwest China from 2018 to 2019. CMEC collected information on the participants, including socio-demographic data, lifestyle habits, and health-related backgrounds through verbal interviews, then assessed anthropometric data, biological samples (blood, urine and saliva) and imaging data.

    Researchers have found that long-term exposure to ambient air pollution may increase the risks of MAFLD, especially in men, smokers and alcohol drinkers, and those who follow a high-fat diet. . Their results, published in the Journal of hepatology, have found that unhealthy lifestyle behaviors and excessive fat accumulation in the abdominal area can also exacerbate the harmful effects. The investigators thus propose that air pollution be recognized as a modifiable risk factor for MAFLD.

    “Our findings add to the growing evidence for the detrimental effects of environmental pollution on metabolic function and associated organs,” said Dr Zhao and his co-investigators. “However, physical activity does not appear to alter the associations between air pollution and MAFLD. We suggest that future studies explore whether the timing, intensity and form of physical activity may mitigate the effects. harmful air pollution.

    Meanwhile, researchers from Nanyang Technological University, Singapore (NTU Singapore) and Chinese University of Hong Kong have linked increased air pollution to a slight increase in cases of pulmonary adenocarcinoma (LADC) – a type of cancer in which research suggests genetic, environmental, and lifestyle factors play a role . The team’s study, published in the journal Atmospheric environment, also concluded that lower overall tobacco consumption globally is statistically linked to a lower number of people who contract pulmonary squamous cell carcinoma (LSCC), which is often linked to a history of smoking.

    The study showed that a concentration of 0.1 μg / m3 The increase in black carbon (soot) in the Earth’s atmosphere is associated with a 12% increase in the incidence of LADC globally. Carbon black is a pollutant classified as PM2.5 (airborne particulate matter less than 2.5 m in diameter), and the research team found that it increased globally by 3.6 g / m3 annually from 1990 to 2012. The incidence of LADC is particularly significant in Asia, where black carbon emissions (11.9 μg / m3/ year) and sulfate (35.4 μg / m3/ year) have increased.

    “In our study, we were able to determine that the worldwide increase in pulmonary adenocarcinoma is likely associated with air pollution,” said study director Professor Joseph Sung, senior vice president of NTU (Health and Life Sciences). “Over the past several decades, it has still not been clear why we are seeing more women and more non-smokers developing lung cancer around the world. Our study highlights the importance of environmental factors in the causation of specific types of lung cancer.

    The link between the pollutant and the incidence of LADC was found to be stronger in women than in men. Overall a 0.1 μg / m3 the annual increase in carbon black was associated with a 14% increase in LADC in women, compared to 9% in men. The relationship between air pollutants and LADC also varied across continents; in North America, a 0.1 μg / m3 The increase in carbon black was linked to a 10% increase in LADC cases, compared to 7% in Europe.

    Meanwhile, a 1% drop in smoking prevalence has been associated with a 9% drop in the incidence of LSCC globally, with the number of smokers globally declining by nearly 6% from 1990 to 2012. However, a positive association between smoking and LSCC was demonstrated for women in Asia, North America and Oceania, where a 1% increase in the number of smokers was associated with a 12% increase in cancer in women. these geographic regions. Scientists explained that despite a lower overall percentage of smokers in the world, there were more smokers in the world due to massive population growth from 1980 to 2012, causing the number of female smokers to increase by 7%.

    “The results of this study should warn us that air pollution should be better controlled to protect health and prevent premature death from lung cancer or related diseases, especially in populations who live near urban areas, which are known to experience high levels of pollutant emissions. “said Professor Sung.

    “Our results underscore the urgent need for further research into how pollutants such as carbon black and sulfate lead to the development of pulmonary adenocarcinoma, and for international leaders and experts to consider mitigation strategies. air pollution. “

    Associate Professor Steve Yim, the study’s first author, added, “While national environmental regulators routinely measure and report fine particle levels, our results underscore the importance of measuring individual types. particles, in particular carbon black. The information would be useful in formulating effective emission control policies, supporting sustainable development policies.

    The team plans to conduct further research to study the functions of carbon black and sulfate in the development of LADC, which could lead to new studies to fight the resurgence of cancer. The team also hopes to explore other pollutants that could be linked to lung cancer.

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    Can non-invasive medical devices help stop liver disease? https://rogalevich.org/can-non-invasive-medical-devices-help-stop-liver-disease/ Tue, 11 Jan 2022 18:15:52 +0000 https://rogalevich.org/can-non-invasive-medical-devices-help-stop-liver-disease/ A silent epidemic of liver disease is sweeping the country and the world through an increase in chronic liver disease, such as non-alcoholic fatty liver disease (NAFLD) and its most severe form, non-alcoholic steatohepatitis (NASH). NASH can lead to advanced fibrosis and liver cancer, liver transplantation and increased risk of cardiovascular events and all-cause mortality, […]]]>

    A silent epidemic of liver disease is sweeping the country and the world through an increase in chronic liver disease, such as non-alcoholic fatty liver disease (NAFLD) and its most severe form, non-alcoholic steatohepatitis (NASH). NASH can lead to advanced fibrosis and liver cancer, liver transplantation and increased risk of cardiovascular events and all-cause mortality, while NAFLD is one of the most common causes of liver disease in states -United. Experts say that around 24% of US adults have NAFLD and about 1.5% to 6.5% of US adults have NASH.

    Fortunately, liver disease can often be reversed with early diagnosis and intervention using medical devices called non-invasive tests (NITs) to help in the management of patients with liver disease. The most promising NIT is transient vibration-controlled elastography (VCTE) technology, including measurement of liver stiffness (LSM) by transient elastography (TE), controlled attenuation parameter (CAP) and Spleen stiffness measurement (SSM) as an additional NIT to further improve risk stratification and refine the risk of high-risk varicose veins.

    Studies show that detecting and monitoring liver disease using VCTE is a non-invasive, convenient, and cost-effective way for clinicians to quantify liver tissue stiffness and estimate point-of-care liver fat.

    Focus on VCTE technology

    VCTE combines standardization, clinical performance and accessibility for the early identification of patients, whether in primary care, diabetes clinic or liver clinic, and for the management of patients with liver disease advanced portal hypertension and risk stratification for hepatocellular carcinoma (HCC).

    VCTE technology is essential for detecting and monitoring NAFLD / NASH, alcoholic liver disease (ALD), hepatitis C virus (including post-sustained virologic response [PSVR]), primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) and autoimmune hepatitis (HAI) in at-risk populations such as patients with metabolic risk factors and / or harmful alcohol consumption . VCTE technology also offers high value for comprehensive liver health management. This is important given the prevalence and associated costs of underdiagnosed liver disease.

    Prevalence and costs of liver disease

    Rates of liver damage have been linked to the alarming increase in obesity among adults in the United States and around the world. In 2000, 30.5% of American adults were obese – a body mass index of 30 or higher– which increased in 2015-2016 and led to an increase in diabetes, cardiovascular disease and certain cancers. In 2017-2018, the obesity rate reached 42.4%—Passing 40% for the first time.

    Obesity can be devastating to vital organs, causing insulin resistance which leads to a build-up of sugar in the blood and increases the amount of free fatty acids circulating in the blood and liver cells. Common in people with type 2 diabetes, the accumulation of fat in the liver increases the risk of liver fibrosis, cirrhosis, liver cancer, and death.

    Costs

    Liver damage is now linked to more than $ 100 billion in annual direct costs. A recent study among Medicare Advantage plans found that the annual cost of NAFLD was $ 9,062 for a new diagnosis and $ 5,363 for long-term management versus $ 4,111 per paired check-up. These costs relate to hospitalization and outpatient appointments, emergency department visits, organ transplants, medical procedures or new diagnoses, new medications or changes to existing medications and mortality.

    Estimates show that 357 million people will have NASH globally by 2030. Since NAFLD and NASH are so closely linked to obesity, diabetes, and lifestyle, a preventative approach to patient engagement is needed to encourage more positive lifestyle behavior changes.

    Addressing behavior change with medical devices

    For many patients, diet and exercise can make all the difference. In fact, a 3% reduction in body weight has been associated with an inversion of fat in the liver, while a reduction of over seven% can resolve NASH in many patients.

    The progression of liver disease is usually slow, giving patients the opportunity to be well managed by primary care physicians. This has prompted a growing number of healthcare providers to adopt VCTE tools to help stop or reverse liver damage in patients at risk.

    Stakeholders could benefit from a VCTE tool that provides test results to help monitor lifestyle modification. The tool is also expected to offer consistent quantitative results to allow clinics to monitor fatty liver disease and provide feedback to patients on changes in their diet and exercise. It is also important that a VCTE tool integrates with EHRs for automatic downloading and storage of exam results to save time, secure data and improve patient follow-up.

    The bottom line: As a medical device, a VCTE tool can help fight the epidemic of liver disease, adding value to a practice, improving patient satisfaction, improving outcomes and playing a role. role in creating a more sustainable health system.

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    Action Madrigal: a powerful catalyst on the way (NASDAQ: MDGL) https://rogalevich.org/action-madrigal-a-powerful-catalyst-on-the-way-nasdaq-mdgl/ Sun, 09 Jan 2022 10:46:00 +0000 https://rogalevich.org/action-madrigal-a-powerful-catalyst-on-the-way-nasdaq-mdgl/ Natali_Mis / iStock via Getty Images Opportunities rarely present themselves. When it’s raining gold, take out the bucket, not the thimble – Warren Buffett In accordance with conventional wisdom, most traders and investors prefer to buy stocks in a bull market. Contrary to popular belief, I firmly believe that the best time to build wealth […]]]>


    Natali_Mis / iStock via Getty Images

    Pharmaceutical Madrigal

    Opportunities rarely present themselves. When it’s raining gold, take out the bucket, not the thimble – Warren Buffett

    In accordance with conventional wisdom, most traders and investors prefer to buy stocks in a bull market. Contrary to popular belief, I firmly believe that the best time to build wealth is to invest in a bear market. Now that’s easier said than done because you have to overcome your most powerful human emotion (ie fear).

    That being said, I would like to come back to Madrigal Pharmaceuticals’ investment thesis. (NASDAQ: MDGL). As of 2H this year, Madrigal shares lost about 40% of the gains. After all, this stock is feeling the downward pressure in the Biotech Bear 2021 market. Interestingly, the fundamentals are intact. Plus, there’s a powerful data catalyst to potentially galvanize stocks to a new high next year. In this research, I will provide a fundamental update on Madrigal and provide my expectations on this Philip Fisher Growth Equity.

    Stock of madrigalsFigure 1: Madrigal map (Source: Stock charts)

    About the company

    As usual, I will present a brief overview of the company for new investors. If you are familiar with the business, you should move on to the next section. Based in Conshohocken, Pa., Madrigal is focused on innovating and commercializing stellar medicine to address the unmet needs of heart and liver disease.

    By performing a laser beam-centric approach, Madrigal only innovates two potent drugs for non-alcoholic steatohepatitis (i.e., NASH) and related conditions. As a jewel in the crown, resmetirom (i.e. Resme) is a thyroid hormone receptor beta (THR-B) designed to treat NASH. Because of the solid data I’m going to talk about, it is likely to become the first drug approved for this untapped market, NASH.

    Madrigal Pharmaceuticals PipelineFigure 2: Therapeutic pipeline (Source: Madrigal)

    Resme for NASH

    As you can see, Resme is special because of its mechanism of action (i.e. MOA). As a B-THR activator, Resme works by increasing the liver’s basal metabolic rate to burn excess liver fat. By increasing the power of the organic fat-burning oven, Resme promotes the liver’s innate regenerative ability to heal itself from NASH.

    Notably, there is no better time than now for Resme to enter the NASH market. As part of the spectrum of non-alcoholic fatty liver disease (NAFLD), NASH is very common. Statistics has shown that 25% of adults in the United States have NAFLD. Of that, 20% are advanced toward NASH (i.e. 5% of the total adult US population). With a growth of 58.64% CAGAR, the NASH market is expected to reach $ 180.09 billion by 2028. So it’s a no-brainer, it’s a gargantuan market.

    Madrigal - Fatty liver diseaseFigure 3: Fatty liver disease (Source: American Liver Foundation)

    Robust preliminary data

    Back in November, Madrigal present stellar data from its phase 3 MAESTRO-NAFLD-1 at the 2021 meeting of the American Association for the Study of Liver Diseases (AASLD). Notably, the presentation reported the final reading of the 52-week open-label portion of the study that evaluated the therapeutic efficacy and safety of Resme in 171 patients with suspected NASH (as defined by non-invasive testing) .

    From Figure 2 below, you can see that there was a sustained reduction in liver fat and liver volume as measured by imaging modalities (MRE and FibroScan). As supporting evidence for efficacy, Figure 3 also demonstrated a reduction in liver enzymes (i.e. AST, ALT, and GGT). As you can see, the more these enzymes are reduced, the greater the improvement in liver function. After all, a diseased or damaged liver would release more of these enzymes. Overall, the 100 mg of Resme per day is well tolerated. Delighted with the results, the CMO (Dr. Becky Taub) remark,

    The complete 52-week open-label results of MAESTRO-NAFLD-1 presented at the Liver Meeting 2021 demonstrate Resme’s ability to potently reduce hepatic fat and liver volume in all subgroups of patients with NASH, including patients treated stably with anti-diabetic drugs such as GLP. -1 SGLT2 agonists and inhibitors. The reduction in liver volume may be explained in part by the reduction in liver fat, but is also likely due to other factors related to the mode of action of resmetirom, potentially including effects on inflammation. Consistent with previous studies, there was a low dropout rate due to side effects without changes in the central axis of thyroid hormones or bone mineral density.

    Madrigal Pharmaceuticals - Open Part of Phase 3 MAESTRO-NAFLD

    Figure 4: Open part of Phase 3 MAESTRO-NAFLD-1 (Source: Madrigal)

    Upcoming catalysts

    Now, critics can argue that the results of the open aspects of MAESTRO-NAFLD-1 are not as significant. In other words, the open-ended aspect subjected the study to potential bias. Due to the merits of his MOA, I respond that Resme is a great drug that will prove itself next year.

    In Q1 2022, Madrigal is projected to report additional first-line data from the “blind arm” of the aforementioned study. With most likely positive results, Resme is poised to allay the doubts of the investment community. Better yet, the company will also release additional data for MAESTRO-NASH in the third quarter.

    Based on my integrated system of forecast, I assigned a 70% (i.e. strongly favorable) probability of posting positive data. My rationale stems from my intuition, years of forecasting experience, Resme’s MOA, and past data publication as we mentioned. Put simply, you can anticipate two powerful data catalysts next year that are likely to move the needle on this title. And if it is positive, you can expect Madrigal to file an NDA for expedited approval sometime in 2H 2022.

    Madrigal - MAESTRO-NAFLD-1

    Figure 5: Catalyst events (Source: Madrigal)

    Financial evaluation

    Just as you would get an annual medical check-up for your well-being, it is important to check the financial health of your inventory. For example, your health is affected by “blood flow” because the viability of your stock depends on “cash flow”. With this in mind, I will analyze the 3Q 2021 report on results for the period ended September 30.

    Like other pre-market biotech companies, Madrigal has yet to generate revenue. Therefore, you need to focus on other meaningful metrics. On that note, there was $ 54.8 million in research and development (R&D) compared to $ 53.2 million for the same period a year earlier. I welcome the trend of increasing R&D because the capital invested today can turn into successful profits tomorrow. After all, you have to plant a tree to enjoy its fruit.

    Additionally, there were net losses of $ 63.1 million ($ 3.79 per share) versus $ 57.9 million ($ 3.75 per share) for the same comparison. On a per share basis, net income depreciated slightly by 1.0%. This makes sense since R&D spending is a bit higher this quarter.

    Madrigal Pharmaceuticals FinancesFigure 6: Key financial indicators (Source: Madrigal)

    Regarding the balance sheet, there was $ 299.1 million in cash, equivalents and investments. Compared to quarterly operating expenses of $ 63.1 million, there is expected to be sufficient capital to fund operations through 4Q 2022. For similar biotech companies, the cash position is essentially adequate. I generally want to see a business have at least four quarter-track cash.

    On balance, you should check if Madrigal is a serial diluter. A business that is serially diluted will render your investment virtually worthless. Since the outstanding shares have gone from 15.4 million to 16.6 million, my calculations show an annual dilution of 7.7%. At this rate, Madrigal easily crossed my 30% threshold for a profitable investment.

    Potential risks

    Since investment research is an imperfect science, there are always risks associated with an investment, no matter how strong. At this point in its growth cycle, the most important concern for Madrigal is whether the next data report for MAESTRO-NAFLD-1 and MAESTRO-NASH will produce positive results. As I am optimistic about the results, I assigned the corresponding risk of 35% negative results.

    If the clinical binary fails, you can expect your stock to drop by 70% and vice versa. The higher magnitude of the depreciation is due to the fact that the entire Madrigal pipeline is tied to the success of Resme. That aside, there are fears that Madrigal is growing too aggressively and thus faces a potential cash flow constraint.

    Conclusion

    Overall I maintain my strong buy recommendation on Madrigal but have upgraded the star rating to 5/5. As Madrigal Pharmaceuticals harnesses the therapeutic power of Resme, the company is poised to make NASH history. There is currently no approved drug to treat this silent killer. Considering the sheer size of the $ 180 billion market, any drug first approved in this niche would have a high probability of becoming a blockbuster. After all, there is no other choice. From a MOA and disease context perspective, there is currently no other drug in development that can outweigh Resme. Early data from the open arm of MAESTRO-NAFLD-1 was strong.

    Going forward, you can anticipate solid data for the blind arm as early as next January. In the third trimester, there are data from MAESTRO-NASH. If positive, you are likely to profit from a robust rally that you expected from this fairness


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    Exploring the growing burden of liver disease https://rogalevich.org/exploring-the-growing-burden-of-liver-disease/ Fri, 07 Jan 2022 14:21:13 +0000 https://rogalevich.org/exploring-the-growing-burden-of-liver-disease/ © iStock / magicmine With one in five people at risk for developing liver disease, Dr Michael Lutz discusses what can be done to combat this growing threat. According to the British Liver Trust, liver disease is the leading cause of death in adults aged 35 to 49. Yet while this statistic is indeed shocking, […]]]>


    © iStock / magicmine

    With one in five people at risk for developing liver disease, Dr Michael Lutz discusses what can be done to combat this growing threat.

    According to the British Liver Trust, liver disease is the leading cause of death in adults aged 35 to 49. Yet while this statistic is indeed shocking, it is equally disturbing to read that 90% of cases of liver disease are in fact preventable. Our liver is an integral part of our overall well-being, responsible for over 500 essential functions in the body, such as helping us detoxify harmful substances in our blood, process food, regulate hormones and fight infections.

    Excess alcohol, a diet rich in processed foods, and sedentary behavior are some of the main risk factors associated with liver disease. the liver is severely damaged. Talk to Health Europe, Dr Michael Lutz, CEO and Managing Director of HepaRegenix, reflects on the growing burden of disease, the challenges of diagnostic procedures, and the need for reliable and innovative therapies that can help patients with acute and chronic liver problems.

    Can you describe some common types of liver disease and their current burden on health systems?

    There are a number of diseases related to the liver and two key factors that can strongly influence their development: food and alcohol, or a combination of both. As the disease progresses, the first stages of deterioration are called non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). These define a range of conditions caused by a buildup of fat in the liver and are commonly seen in overweight people. NAFLD / NASH has four key stages (F1-F4), each with different clinical manifestations and requiring different diagnostic procedures. As the liver becomes inflamed you may see the first signs of steatosis where fat builds up in liver cells (F1), and if left untreated or undiagnosed it may progress. in fibrosis which can cause scarring of the liver and adjacent blood vessels (F2).

    The early stages of liver disease are called non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH) © iStock / Jan-Otto

    The most severe cases of liver disease are stage F3 (advanced liver fibrosis) and stage F4 (cirrhosis). Also known as end-stage liver disease, cirrhosis manifests as scarring and irregular lumps or nodules that can affect the functionality of the liver. There are two types of cirrhosis called “compensated” and “decompensated”. One of the main difficulties at this stage of liver disease is that patients who have compensated cirrhosis may not have any symptoms because their liver is able to function relatively well despite the damage. Conversely, the decompensated stage means the damage to the liver is so severe that it cannot function properly, which in turn can lead to many other health complications, including hepatic encephalopathy and bleeding varicose veins. . At this point, patients would need a liver transplant within two to three years.

    Patients with advanced fibrosis, or even early stage cirrhosis, may be stable for 10 to 20 years. However, the impact of other health problems incurred, such as hepatic encephalopathy, can lead to deterioration of the liver, as well as other organs, and lead to acute liver failure.

    Are there certain demographics or groups that are particularly susceptible to the disease or is lifestyle the main driver of the disease?

    The impact of diet and lifestyle on the liver has been well documented for many years. There are reports that have hinted at fast food as the source of the next US pandemic and that over the next 10 to 20 years there will be a huge increase in the number of people with non-alcoholic steatohepatitis (NASH). , advanced stage fibrosis or cirrhosis. This means that there may be an organ shortage as more people will need a liver transplant.

    The impact of the COVID-19 pandemic has also seen a substantial increase in the number of people turning to alcohol to overcome the ‘COVID blues’, particularly in the UK and US.

    Can you describe some of the main challenges associated with diagnosis and screening? Should more be done to raise awareness?

    Diagnosing the severity of the fibrosis or cirrhosis would require a liver biopsy and subsequent histopathological evaluations, which can be very difficult to determine where to do the liver biopsy in order to get a clear and valid result.

    Although NASH can create opportunities for innovation, for regulatory reasons, many pharmaceutical companies have failed in advanced NASH trials due to the difficult nature of liver biopsies and histopathology. Our company is part of the Liver Forum which was created by the pharmaceutical industry and a few other partners to facilitate the development of drugs for the treatment of liver disease. Last year there was a session where people said that histopaths, and the results are like rolling the dice; three pathologists can take a sample, and each can give different results.

    In terms of awareness, there are effective initiatives to encourage healthier lifestyles; we have seen a gradual decline in the number of people who smoke over the past 10 to 15 years and we are now seeing similar initiatives regarding sugar taxes. Advocating a healthy lifestyle that incorporates more exercise, less alcohol and red meat is a starting point, but in some countries like the United States, the scale of liver disease is increasing so rapidly that interventions are urgently needed. In the past 10 years alone, cases of liver disease in the United States have increased by around 25% and we expect this to continue to rise if left unchecked.

    On your website, you state that there is a huge unmet medical need, mainly due to the lack of treatment options. Can you share any innovations or recent developments that could improve the success rate of treatment for liver disease?

    When I joined HepaRegeniX in 2019, the NASH space was very crowded with over 200 companies developing treatments. However, since then many of these companies’ attempts have failed and they have left the NASH space. Our company has embarked on other projects focused on more advanced liver diseases. In the early stages of some liver diseases, regulators are still convinced that if you make changes to your diet and lifestyle, you can stop the disease and essentially heal yourself. Therefore, they are reluctant to motivate and fund companies to create drugs for these patients. Supporting patients with acute or chronic liver failure is another story, and more and more people will need this type of advanced care. We already hear the term “liver tsunami” reflecting the rapid increase in the number of people in need of treatment. Likewise, some reports predict that liver cancer will be the most important cancer over the next 20 years.

    There are still companies developing treatments for NASH as well as those trying to “cleanse” fat from the liver or reduce the impact and early symptoms of NAFLD, including treatments for obesity. There are also companies that try to roll back and prevent fibrosis from growing further. Regenerative medicine companies like ours are studying the more severe stages of liver disease to support patients who need it and that is our goal with upcoming clinical trials.

    In development, HepaRegenix only works on advanced liver diseases. Can you explain how your therapeutic approach differs from currently approved therapies and more advanced compounds currently in clinical development?

    Current therapies for chronic liver disease focus on reducing or eliminating harmful exogenous agents and thus may slow the progression of the disease. For terminal liver disease, transplantation is currently the only curative option. Currently, no therapy can restore the almost infinite regenerative capacity of healthy liver cells. Yet this is exactly the approach we follow at HepaRegeniX: we aim to unlock the regenerative capacity of hepatocytes. Our target is the Mitogen Activated Protein (MAP) Kinase Kinase 4 – in short: MKK4. The foundations of this “first-in-class” approach were laid in the laboratory of Professor Lars Zender at the University Hospital of Tübingen. In cooperation, we have developed a small molecule platform of MKK4 inhibitors. From extensive preclinical studies, we know that restoration of regenerative capacity through inhibition of MKK4 is possible even in severely affected livers. In fact, the evidence we were able to gather in acute and chronic liver disease was very convincing and fully confirmed the therapeutic rationale. More recently, we reported significant benefits in terms of survival and improvement of key liver function parameters in collaboration with the Mayo Clinic. As we embark on our Phase 1 First-In-Human trial which began in August 2021, we see the great potential of MKK4 to treat patients with advanced liver disease.

    Dr Michael Lutz
    CEO / Managing Director
    HepaRegeniX
    www.heparegenix.com

    This article is taken from issue 20 of Europa Health Quarterly. Click on here to get your free subscription today.




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