Lipid Disorders

The high-density lipoprotein particle’s complexity as a mediator of cardiovascular risk was on display in a case-control study that, the researchers say, points to its anti-inflammatory capacity as potentially a worthy addition to standard CV risk assessments.

A measure of HDL anti-inflammatory capacity in a prospective community cohort was inversely related to future CV risk independent of HDL’s role in cholesterol transport, total cholesterol, and other established biomarkers, as well as any lipid-modifying therapy.

The current analysis “identified an impaired HDL anti-inflammatory capacity as a functional metric prospectively associated with increased cardiovascular risk in the general population,” observed the authors of the study, published April 12, 2021, in Circulation, led by Congzhuo Jia, MD, University of Groningen (the Netherlands).

“In contrast with the cholesterol efflux function of HDL that tracks moderately with HDL cholesterol levels,” they wrote, HDL anti-inflammatory capacity was not significantly correlated with actual levels of the lipoprotein or a major constituent, apolipoprotein A1 (apoA1). Nor was it correlated with levels of a more generalized inflammatory biomarker, C-reactive protein by high-sensitivity assay (hsCRP).

In a test of its independence as a prognosticator, HDL anti-inflammatory capacity significantly and meaningfully improved prediction of CV events in the study after it was added to the familiar Framingham risk equations.

Measurement of HDL anti-inflammatory properties, therefore, has the potential to improve current CV risk assessments in people without clinical heart disease, the authors proposed.

The study “adds to our understanding of the potential cardioprotective role of HDL,” Michael Miller, MD, University of Maryland, Baltimore, said in an interview.

“We’ve known for some time that HDL has anti-inflammatory properties in vitro, and my understanding is this is the first study to assess these anti-inflammatory properties in a clinical trial,” said Dr. Miller, who studies lipid metabolism and directs the Center for Preventive Cardiology at his center but isn’t an author of the report.

The study is part of a long line of research aiming to “untangle the complexities of HDL and try to get a better handle as to the properties that make it cardioprotective,” he said. For example, “high levels are not always associated with cardioprotection, and low levels don’t always imply increased risk.”

The current findings highlight a quality of HDL that might be prognostic but also independent of its concentrations, apoA1 content, or cholesterol efflux capacity, Dr. Miller noted. That makes HDL anti-inflammatory capacity a “promising feature” of HDL that, if confirmed in further studies, could potentially be brought into the mainstream for CV risk prediction. “But it’s too premature at this time.”

The study of participants in the population-based PREVEND cohort study compared 340 patients with a first CV event – CV death, ischemic heart disease, nonfatal MI, or coronary revascularization – over a median of about 10 years with the same number of participants without such events. The two cohorts of people from the same city in the Netherlands had been matched according to sex, smoking status, age, and HDL cholesterol levels at baseline.

No measured clinical or laboratory value, the group wrote, was significantly correlated with HDL anti-inflammatory capacity, defined here as ability to suppress vascular cell adhesion molecule-1 (VCAM-1) mRNA expression as induced by tumor necrosis factor–alpha in endothelial cells in vitro.

HDL anti-inflammatory capacity was significantly lower in the case cohort, compared with the control cohort (P < .001), and was inversely related to new CV events, at an odds ratio per 1 standard deviation of 0.74 (95% confidence interval, 0.61-0.90; P = .002). Covariate adjustments included body mass index; alcohol intake; diabetes and hypertension status; use of lipid-lowering medicine; levels of total cholesterol, apoA1, triglyceride, and hsCRP; and measures of renal function.

No significant association was seen between HDL anti-inflammatory capacity and cholesterol efflux capacity (coefficient of correlation, −0.02; P > .05). But both metrics were independently associated with CV disease events. The OR per 1 standard deviation was 0.74 (95% CI, 0.61-0.90; P = .002) for cholesterol efflux capacity and 0.66 (95% CI, 0.54-0.81; P < .001) for HDL anti-inflammatory capacity.

Adding HDL anti-inflammatory capacity to the Framingham risk score significantly improved its predictive power; its likelihood-ratio statistic rose from 10.50 to 20.40 (P = .002), the group wrote. The addition of cholesterol efflux capacity further elevated the risk score’s likelihood-ratio statistic to 32.84 (P = .0005).

The analysis has all the limitations of a case-control study, Dr. Miller said, but it does “show a potential reasonable association” between anti-inflammatory capacity and CV risk “that needs to be taken to the next level.”

For example, it could be explored in a controlled trial that tracks anti-inflammatory capacity in individuals who receive an intervention that is likely to improve the biomarker – such as weight loss, he proposed – and follows them for clinical outcomes.

“If you want to elevate the stature of the anti-inflammatory index,” Dr. Miller said, “you will need to show that it’s clinically meaningful.”

Dr. Jia reported no conflicts. Dr. Miller has no relevant disclosures.

A version of this article first appeared on Medscape.com.

The high-density lipoprotein particle’s complexity as a mediator of cardiovascular risk was on display in a case-control study that, the researchers say, points to its anti-inflammatory capacity as potentially a worthy addition to standard CV risk assessments.

A measure of HDL anti-inflammatory capacity in a prospective community cohort was inversely related to future CV risk independent of HDL’s role in cholesterol transport, total cholesterol, and other established biomarkers, as well as any lipid-modifying therapy.

The current analysis “identified an impaired HDL anti-inflammatory capacity as a functional metric prospectively associated with increased cardiovascular risk in the general population,” observed the authors of the study, published April 12, 2021, in Circulation, led by Congzhuo Jia, MD, University of Groningen (the Netherlands).

“In contrast with the cholesterol efflux function of HDL that tracks moderately with HDL cholesterol levels,” they wrote, HDL anti-inflammatory capacity was not significantly correlated with actual levels of the lipoprotein or a major constituent, apolipoprotein A1 (apoA1). Nor was it correlated with levels of a more generalized inflammatory biomarker, C-reactive protein by high-sensitivity assay (hsCRP).

In a test of its independence as a prognosticator, HDL anti-inflammatory capacity significantly and meaningfully improved prediction of CV events in the study after it was added to the familiar Framingham risk equations.

Measurement of HDL anti-inflammatory properties, therefore, has the potential to improve current CV risk assessments in people without clinical heart disease, the authors proposed.

The study “adds to our understanding of the potential cardioprotective role of HDL,” Michael Miller, MD, University of Maryland, Baltimore, said in an interview.

“We’ve known for some time that HDL has anti-inflammatory properties in vitro, and my understanding is this is the first study to assess these anti-inflammatory properties in a clinical trial,” said Dr. Miller, who studies lipid metabolism and directs the Center for Preventive Cardiology at his center but isn’t an author of the report.

The study is part of a long line of research aiming to “untangle the complexities of HDL and try to get a better handle as to the properties that make it cardioprotective,” he said. For example, “high levels are not always associated with cardioprotection, and low levels don’t always imply increased risk.”

The current findings highlight a quality of HDL that might be prognostic but also independent of its concentrations, apoA1 content, or cholesterol efflux capacity, Dr. Miller noted. That makes HDL anti-inflammatory capacity a “promising feature” of HDL that, if confirmed in further studies, could potentially be brought into the mainstream for CV risk prediction. “But it’s too premature at this time.”

The study of participants in the population-based PREVEND cohort study compared 340 patients with a first CV event – CV death, ischemic heart disease, nonfatal MI, or coronary revascularization – over a median of about 10 years with the same number of participants without such events. The two cohorts of people from the same city in the Netherlands had been matched according to sex, smoking status, age, and HDL cholesterol levels at baseline.

No measured clinical or laboratory value, the group wrote, was significantly correlated with HDL anti-inflammatory capacity, defined here as ability to suppress vascular cell adhesion molecule-1 (VCAM-1) mRNA expression as induced by tumor necrosis factor–alpha in endothelial cells in vitro.

HDL anti-inflammatory capacity was significantly lower in the case cohort, compared with the control cohort (P < .001), and was inversely related to new CV events, at an odds ratio per 1 standard deviation of 0.74 (95% confidence interval, 0.61-0.90; P = .002). Covariate adjustments included body mass index; alcohol intake; diabetes and hypertension status; use of lipid-lowering medicine; levels of total cholesterol, apoA1, triglyceride, and hsCRP; and measures of renal function.

No significant association was seen between HDL anti-inflammatory capacity and cholesterol efflux capacity (coefficient of correlation, −0.02; P > .05). But both metrics were independently associated with CV disease events. The OR per 1 standard deviation was 0.74 (95% CI, 0.61-0.90; P = .002) for cholesterol efflux capacity and 0.66 (95% CI, 0.54-0.81; P < .001) for HDL anti-inflammatory capacity.

Adding HDL anti-inflammatory capacity to the Framingham risk score significantly improved its predictive power; its likelihood-ratio statistic rose from 10.50 to 20.40 (P = .002), the group wrote. The addition of cholesterol efflux capacity further elevated the risk score’s likelihood-ratio statistic to 32.84 (P = .0005).

The analysis has all the limitations of a case-control study, Dr. Miller said, but it does “show a potential reasonable association” between anti-inflammatory capacity and CV risk “that needs to be taken to the next level.”

For example, it could be explored in a controlled trial that tracks anti-inflammatory capacity in individuals who receive an intervention that is likely to improve the biomarker – such as weight loss, he proposed – and follows them for clinical outcomes.

“If you want to elevate the stature of the anti-inflammatory index,” Dr. Miller said, “you will need to show that it’s clinically meaningful.”

Dr. Jia reported no conflicts. Dr. Miller has no relevant disclosures.

A version of this article first appeared on Medscape.com.

The high-density lipoprotein particle’s complexity as a mediator of cardiovascular risk was on display in a case-control study that, the researchers say, points to its anti-inflammatory capacity as potentially a worthy addition to standard CV risk assessments.

A measure of HDL anti-inflammatory capacity in a prospective community cohort was inversely related to future CV risk independent of HDL’s role in cholesterol transport, total cholesterol, and other established biomarkers, as well as any lipid-modifying therapy.

The current analysis “identified an impaired HDL anti-inflammatory capacity as a functional metric prospectively associated with increased cardiovascular risk in the general population,” observed the authors of the study, published April 12, 2021, in Circulation, led by Congzhuo Jia, MD, University of Groningen (the Netherlands).

“In contrast with the cholesterol efflux function of HDL that tracks moderately with HDL cholesterol levels,” they wrote, HDL anti-inflammatory capacity was not significantly correlated with actual levels of the lipoprotein or a major constituent, apolipoprotein A1 (apoA1). Nor was it correlated with levels of a more generalized inflammatory biomarker, C-reactive protein by high-sensitivity assay (hsCRP).

In a test of its independence as a prognosticator, HDL anti-inflammatory capacity significantly and meaningfully improved prediction of CV events in the study after it was added to the familiar Framingham risk equations.

Measurement of HDL anti-inflammatory properties, therefore, has the potential to improve current CV risk assessments in people without clinical heart disease, the authors proposed.

The study “adds to our understanding of the potential cardioprotective role of HDL,” Michael Miller, MD, University of Maryland, Baltimore, said in an interview.

“We’ve known for some time that HDL has anti-inflammatory properties in vitro, and my understanding is this is the first study to assess these anti-inflammatory properties in a clinical trial,” said Dr. Miller, who studies lipid metabolism and directs the Center for Preventive Cardiology at his center but isn’t an author of the report.

The study is part of a long line of research aiming to “untangle the complexities of HDL and try to get a better handle as to the properties that make it cardioprotective,” he said. For example, “high levels are not always associated with cardioprotection, and low levels don’t always imply increased risk.”

The current findings highlight a quality of HDL that might be prognostic but also independent of its concentrations, apoA1 content, or cholesterol efflux capacity, Dr. Miller noted. That makes HDL anti-inflammatory capacity a “promising feature” of HDL that, if confirmed in further studies, could potentially be brought into the mainstream for CV risk prediction. “But it’s too premature at this time.”

The study of participants in the population-based PREVEND cohort study compared 340 patients with a first CV event – CV death, ischemic heart disease, nonfatal MI, or coronary revascularization – over a median of about 10 years with the same number of participants without such events. The two cohorts of people from the same city in the Netherlands had been matched according to sex, smoking status, age, and HDL cholesterol levels at baseline.

No measured clinical or laboratory value, the group wrote, was significantly correlated with HDL anti-inflammatory capacity, defined here as ability to suppress vascular cell adhesion molecule-1 (VCAM-1) mRNA expression as induced by tumor necrosis factor–alpha in endothelial cells in vitro.

HDL anti-inflammatory capacity was significantly lower in the case cohort, compared with the control cohort (P < .001), and was inversely related to new CV events, at an odds ratio per 1 standard deviation of 0.74 (95% confidence interval, 0.61-0.90; P = .002). Covariate adjustments included body mass index; alcohol intake; diabetes and hypertension status; use of lipid-lowering medicine; levels of total cholesterol, apoA1, triglyceride, and hsCRP; and measures of renal function.

No significant association was seen between HDL anti-inflammatory capacity and cholesterol efflux capacity (coefficient of correlation, −0.02; P > .05). But both metrics were independently associated with CV disease events. The OR per 1 standard deviation was 0.74 (95% CI, 0.61-0.90; P = .002) for cholesterol efflux capacity and 0.66 (95% CI, 0.54-0.81; P < .001) for HDL anti-inflammatory capacity.

Adding HDL anti-inflammatory capacity to the Framingham risk score significantly improved its predictive power; its likelihood-ratio statistic rose from 10.50 to 20.40 (P = .002), the group wrote. The addition of cholesterol efflux capacity further elevated the risk score’s likelihood-ratio statistic to 32.84 (P = .0005).

The analysis has all the limitations of a case-control study, Dr. Miller said, but it does “show a potential reasonable association” between anti-inflammatory capacity and CV risk “that needs to be taken to the next level.”

For example, it could be explored in a controlled trial that tracks anti-inflammatory capacity in individuals who receive an intervention that is likely to improve the biomarker – such as weight loss, he proposed – and follows them for clinical outcomes.

“If you want to elevate the stature of the anti-inflammatory index,” Dr. Miller said, “you will need to show that it’s clinically meaningful.”

Dr. Jia reported no conflicts. Dr. Miller has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Clinicians in pediatrics have noticed a troubling pattern emerge during the pandemic, something that is darkly referred to as “the COVID 19,” or the 19 or more pounds that many of our patients have gained in the past year. This phenomenon has underscored many maxims in pediatric weight management: Mainly that frequent snacking, decreased physical activity, and less parental supervision lead to increased weight gain. But could we be missing another lesson this trend is teaching us? What about the relationship between catastrophe and childhood obesity?

Beyond the increased weight gain with lockdowns, I have observed other evidence in my own practice that childhood trauma or adverse experiences increase obesity. Our electronic medical record system gives an alert when a chart with sensitive information is accessed. One example might be if the patient had been seen at a clinic for children who have been abused. I am heartbroken at how often this happens. Academically, I understand the dire statistics about the incidence of child abuse, but the frequency at which I see this pattern is jarring.

Over the years, one striking correlation became clear among my patient population: Children with obesity were more likely to have been seen in the child abuse clinic than normal-weight peers.

I am far from the only one to have observed this relationship. Television shows focusing on severe obesity, such as “My 600-Pound Life,” often show trauma as both a cause and effect of severe obesity. This theme also became apparent on the show “The Biggest Loser,” which highlighted the difficulty of achieving and maintaining substantial weight loss. If even Hollywood has noticed this association, shouldn’t we be much farther ahead?
 

Pathways to obesity

Adverse childhood experiences (ACE) encompass various causes of child trauma, including abuse or neglect; poverty; household or neighborhood violence; and death, illness, or incarceration of a parent. A pivotal report in 1998 formalized the suspicion that many of us could plainly see: People who suffered ACE have higher incidence of heart disease, COPD, liver disease, incarceration, and drug abuse. For those with six or more ACE, life expectancy averaged 20 years less than those who had none. More recently, a meta-analysis found an odds ratio of 1.46 for adult obesity with known history of childhood trauma.

As a pediatric endocrinologist living in the poorest state of the country, I have clearly observed the correlation between childhood obesity and poverty. While prior generations may have associated child poverty with malnutrition and starvation, we are seeing in modern times that obesity has become a disease of lack. Calorie-dense and processed foods tend to be less expensive, more shelf-stable, and more accessible to people living in both urban and rural food deserts.

I am also a foster mother and have received extensive training in parenting children who have lived through trauma and neglect. For children who have endured food scarcity and deprivation, hoarding food and overeating are expected responses.

But the pathways to abnormal weight gain are myriad and expand beyond binge eating or numbing with food. ACE are particularly troubling because they affect developing brains and the neuroendocrine system; they alter epigenetics and cause heritable changes. Structural brain differences have been evident in the frontopolar cortex, which is linked to centers in the hypothalamus that control appetite. And increased stress raises cortisol release, increases insulin resistance, and alters satiety.
 

Shifting our approach to treatment

The significant cost of ACE is enormous and affects us all. Health professionals in pediatrics must understand these connections to effectively counsel children and their families dealing with obesity. Handing someone a diet plan and lecturing them about weight loss is never effective, but this common tactic is especially cruel if we do not assess for and address underlying pain. Obviously, blame and shame are ineffective motivators for lifestyle change in any circumstance, but these tactics may be especially harmful in the light of childhood trauma.

Screening for ACE is important in every aspect of pediatric care. The presence of obesity, however, should remind us to be more sensitive to the possibility of causative trauma. Clinicians for adults are not off the hook either. Fully 60% of adults suffered ACE and are dealing with the aftermath.

To improve health outcomes across the board, we must screen for trauma and become educated on trauma-informed care. Perhaps the most important first referral for a child suffering ACE and obesity is to a trained counselor or a social worker. Shepherding children through trauma will be more effective for attaining healthy weight than any remedy I can prescribe as an endocrinologist. Furthermore, this is our necessary role as healers. More than ever, we need to approach chronic diseases, including obesity, with the utmost compassion.

A version of this article first appeared on Medscape.com.

Clinicians in pediatrics have noticed a troubling pattern emerge during the pandemic, something that is darkly referred to as “the COVID 19,” or the 19 or more pounds that many of our patients have gained in the past year. This phenomenon has underscored many maxims in pediatric weight management: Mainly that frequent snacking, decreased physical activity, and less parental supervision lead to increased weight gain. But could we be missing another lesson this trend is teaching us? What about the relationship between catastrophe and childhood obesity?

Beyond the increased weight gain with lockdowns, I have observed other evidence in my own practice that childhood trauma or adverse experiences increase obesity. Our electronic medical record system gives an alert when a chart with sensitive information is accessed. One example might be if the patient had been seen at a clinic for children who have been abused. I am heartbroken at how often this happens. Academically, I understand the dire statistics about the incidence of child abuse, but the frequency at which I see this pattern is jarring.

Over the years, one striking correlation became clear among my patient population: Children with obesity were more likely to have been seen in the child abuse clinic than normal-weight peers.

I am far from the only one to have observed this relationship. Television shows focusing on severe obesity, such as “My 600-Pound Life,” often show trauma as both a cause and effect of severe obesity. This theme also became apparent on the show “The Biggest Loser,” which highlighted the difficulty of achieving and maintaining substantial weight loss. If even Hollywood has noticed this association, shouldn’t we be much farther ahead?
 

Pathways to obesity

Adverse childhood experiences (ACE) encompass various causes of child trauma, including abuse or neglect; poverty; household or neighborhood violence; and death, illness, or incarceration of a parent. A pivotal report in 1998 formalized the suspicion that many of us could plainly see: People who suffered ACE have higher incidence of heart disease, COPD, liver disease, incarceration, and drug abuse. For those with six or more ACE, life expectancy averaged 20 years less than those who had none. More recently, a meta-analysis found an odds ratio of 1.46 for adult obesity with known history of childhood trauma.

As a pediatric endocrinologist living in the poorest state of the country, I have clearly observed the correlation between childhood obesity and poverty. While prior generations may have associated child poverty with malnutrition and starvation, we are seeing in modern times that obesity has become a disease of lack. Calorie-dense and processed foods tend to be less expensive, more shelf-stable, and more accessible to people living in both urban and rural food deserts.

I am also a foster mother and have received extensive training in parenting children who have lived through trauma and neglect. For children who have endured food scarcity and deprivation, hoarding food and overeating are expected responses.

But the pathways to abnormal weight gain are myriad and expand beyond binge eating or numbing with food. ACE are particularly troubling because they affect developing brains and the neuroendocrine system; they alter epigenetics and cause heritable changes. Structural brain differences have been evident in the frontopolar cortex, which is linked to centers in the hypothalamus that control appetite. And increased stress raises cortisol release, increases insulin resistance, and alters satiety.
 

Shifting our approach to treatment

The significant cost of ACE is enormous and affects us all. Health professionals in pediatrics must understand these connections to effectively counsel children and their families dealing with obesity. Handing someone a diet plan and lecturing them about weight loss is never effective, but this common tactic is especially cruel if we do not assess for and address underlying pain. Obviously, blame and shame are ineffective motivators for lifestyle change in any circumstance, but these tactics may be especially harmful in the light of childhood trauma.

Screening for ACE is important in every aspect of pediatric care. The presence of obesity, however, should remind us to be more sensitive to the possibility of causative trauma. Clinicians for adults are not off the hook either. Fully 60% of adults suffered ACE and are dealing with the aftermath.

To improve health outcomes across the board, we must screen for trauma and become educated on trauma-informed care. Perhaps the most important first referral for a child suffering ACE and obesity is to a trained counselor or a social worker. Shepherding children through trauma will be more effective for attaining healthy weight than any remedy I can prescribe as an endocrinologist. Furthermore, this is our necessary role as healers. More than ever, we need to approach chronic diseases, including obesity, with the utmost compassion.

A version of this article first appeared on Medscape.com.

Clinicians in pediatrics have noticed a troubling pattern emerge during the pandemic, something that is darkly referred to as “the COVID 19,” or the 19 or more pounds that many of our patients have gained in the past year. This phenomenon has underscored many maxims in pediatric weight management: Mainly that frequent snacking, decreased physical activity, and less parental supervision lead to increased weight gain. But could we be missing another lesson this trend is teaching us? What about the relationship between catastrophe and childhood obesity?

Beyond the increased weight gain with lockdowns, I have observed other evidence in my own practice that childhood trauma or adverse experiences increase obesity. Our electronic medical record system gives an alert when a chart with sensitive information is accessed. One example might be if the patient had been seen at a clinic for children who have been abused. I am heartbroken at how often this happens. Academically, I understand the dire statistics about the incidence of child abuse, but the frequency at which I see this pattern is jarring.

Over the years, one striking correlation became clear among my patient population: Children with obesity were more likely to have been seen in the child abuse clinic than normal-weight peers.

I am far from the only one to have observed this relationship. Television shows focusing on severe obesity, such as “My 600-Pound Life,” often show trauma as both a cause and effect of severe obesity. This theme also became apparent on the show “The Biggest Loser,” which highlighted the difficulty of achieving and maintaining substantial weight loss. If even Hollywood has noticed this association, shouldn’t we be much farther ahead?
 

Pathways to obesity

Adverse childhood experiences (ACE) encompass various causes of child trauma, including abuse or neglect; poverty; household or neighborhood violence; and death, illness, or incarceration of a parent. A pivotal report in 1998 formalized the suspicion that many of us could plainly see: People who suffered ACE have higher incidence of heart disease, COPD, liver disease, incarceration, and drug abuse. For those with six or more ACE, life expectancy averaged 20 years less than those who had none. More recently, a meta-analysis found an odds ratio of 1.46 for adult obesity with known history of childhood trauma.

As a pediatric endocrinologist living in the poorest state of the country, I have clearly observed the correlation between childhood obesity and poverty. While prior generations may have associated child poverty with malnutrition and starvation, we are seeing in modern times that obesity has become a disease of lack. Calorie-dense and processed foods tend to be less expensive, more shelf-stable, and more accessible to people living in both urban and rural food deserts.

I am also a foster mother and have received extensive training in parenting children who have lived through trauma and neglect. For children who have endured food scarcity and deprivation, hoarding food and overeating are expected responses.

But the pathways to abnormal weight gain are myriad and expand beyond binge eating or numbing with food. ACE are particularly troubling because they affect developing brains and the neuroendocrine system; they alter epigenetics and cause heritable changes. Structural brain differences have been evident in the frontopolar cortex, which is linked to centers in the hypothalamus that control appetite. And increased stress raises cortisol release, increases insulin resistance, and alters satiety.
 

Shifting our approach to treatment

The significant cost of ACE is enormous and affects us all. Health professionals in pediatrics must understand these connections to effectively counsel children and their families dealing with obesity. Handing someone a diet plan and lecturing them about weight loss is never effective, but this common tactic is especially cruel if we do not assess for and address underlying pain. Obviously, blame and shame are ineffective motivators for lifestyle change in any circumstance, but these tactics may be especially harmful in the light of childhood trauma.

Screening for ACE is important in every aspect of pediatric care. The presence of obesity, however, should remind us to be more sensitive to the possibility of causative trauma. Clinicians for adults are not off the hook either. Fully 60% of adults suffered ACE and are dealing with the aftermath.

To improve health outcomes across the board, we must screen for trauma and become educated on trauma-informed care. Perhaps the most important first referral for a child suffering ACE and obesity is to a trained counselor or a social worker. Shepherding children through trauma will be more effective for attaining healthy weight than any remedy I can prescribe as an endocrinologist. Furthermore, this is our necessary role as healers. More than ever, we need to approach chronic diseases, including obesity, with the utmost compassion.

A version of this article first appeared on Medscape.com.

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.

Among almost 100,000 patients with severe obesity (body mass index >40 kg/m²) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.

Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.

It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.

“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”

Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.

Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.

Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
 

Rising rates of fatty liver disease, obesity

An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.

NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.

Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.

Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.

Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.

Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.

One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.

Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
 

Does bariatric surgery curb cancer risk in liver disease?

The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.

Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.

Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).

During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.

A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).

The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

Nonalcoholic fatty liver disease (NAFLD) in children is almost always caused by excess body weight, not other etiologies, based on a retrospective analysis of 900 patients.

Just 2% of children with overweight or obesity and suspected NAFLD had other causes of liver disease, and none tested positive for autoimmune hepatitis (AIH), reported lead author Toshifumi Yodoshi, MD, PhD, of Cincinnati Children’s Hospital Medical Center, and colleagues.

“Currently, recommended testing of patients with suspected NAFLD includes ruling out the following conditions: AIH, Wilson disease, hemochromatosis, alpha-1 antitrypsin [A1AT] deficiency, viral hepatitis, celiac disease, and thyroid dysfunction,” the investigators wrote in Pediatrics.

Yet evidence supporting this particular battery of tests is scant; just one previous pediatric study has estimated the prevalence of other liver diseases among children with suspected NAFLD. The study showed that the second-most common etiology, after NAFLD, was AIH, at a rate of 4%.

But “the generalizability of these findings is uncertain,” noted Dr. Yodoshi and colleagues, as the study was conducted at one tertiary center in the western United States, among a population that was predominantly Hispanic.

This uncertainty spurred the present study, which was conducted at two pediatric centers: Cincinnati Children’s Hospital Medical Center (2009-2017) and Yale New Haven (Conn.) Children’s Hospital (2012-2017).

The final analysis involved 900 patients aged 18 years or younger with suspected NAFLD based on hepatic steatosis detected via imaging and/or elevated serum aminotransferases. Demographically, a slight majority of the patients were boys (63%), and approximately one-quarter (26%) were Hispanic. Median BMI z score was 2.45, with three out of four patients (76%) exhibiting severe obesity. Out of 900 patients, 358 (40%) underwent liver biopsy, among whom 46% had confirmed nonalcoholic steatohepatitis.

All patients underwent testing to exclude the aforementioned conditions using various diagnostics, revealing that just 2% of the population had etiologies other than NAFLD. Specifically, 11 children had thyroid dysfunction (1.2%), 3 had celiac disease (0.4%), 3 had A1AT deficiency (0.4%), 1 had hemophagocytic lymphohistiocytosis, and 1 had Hodgkin’s lymphoma. None of the children had Wilson disease, hepatitis B or C, or AIH.

Dr. Yodoshi and colleagues highlighted the latter finding, noting that 13% of the patients had autoantibodies for AIH, but “none met composite criteria.” This contrasts with the previous study from 2013, which found an AIH rate of 4%.

“Nonetheless,” the investigators went on, “NAFLD remains a diagnosis of exclusion, and key conditions that require specific treatments must be ruled out in the workup of patients with suspected NAFLD. In the future, the cost-effectiveness of this approach will need to be investigated.”

Interpreting the findings, Francis E. Rushton, MD, of Beaufort (S.C.) Memorial Hospital emphasized the implications for preventive and interventional health care.

“This study showing an absence of etiologies other than obesity in overweight children with NAFLD provides further impetus for pediatricians to work on both preventive and treatment regimens for weight issues,” Dr. Rushton said. “Linking community-based initiatives focused on adequate nutritional support with pediatric clinical support services is critical in solving issues related to overweight in children. Tracking BMI over time and developing healthy habit goals for patients are key parts of clinical interventions.” 

The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment of obesity through exercise and diet is unquestionably the foundation of care for patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). But drinking at least several cups of coffee a day makes for additional powerful medicine, said Manal F. Abdelmalek, MD, MPH, at the Gastroenterology Updates, IBD, Liver Disease Conference.

s-photo/iStockphoto.com

“I do recommend at least two to three cups of coffee per day for my patients with NAFLD,” said Dr. Abdelmalek, professor of medicine and a gastroenterologist at Duke University, Durham, N.C.

Her thinking on this recommendation has been influenced by a meta-analysis of 16 studies including more than 3,000 coffee drinkers and 132,000 nonconsumers; the meta-analysis concluded that coffee drinkers were 39% less likely to develop cirrhosis. There was evidence of a dose-response effect: Consumers of two or more cups daily had a 47% reduction in the risk of cirrhosis, compared with the nondrinkers, while more modest consumption was associated with a 34% reduction. Moreover, the investigators found that coffee consumption was also associated with a 27% reduction in the likelihood of developing advanced hepatic fibrosis, compared with that of non–coffee drinkers.

“What’s even more provocative is the evidence that coffee decreases risk of hepatocellular carcinoma,” the gastroenterologist said.

She highlighted a U.K. meta-analysis of 18 cohort studies with 2.27 million participants and 2,905 cases, along with 8 case-control studies featuring a collective 1,825 cases and 4,652 controls. The investigators reported that drinking at least two cups of coffee per day was associated with a 35% reduction in the risk of hepatocellular carcinoma independent of a patient’s stage of liver disease or the presence or absence of high alcohol consumption, smoking, obesity, type 2 diabetes, or hepatitis B or C infection.

“This is very impressive data and certainly not something you should ignore,” according to Dr. Abdelmalek.

There is also “fairly strong” data that coffee reduces the risk of developing type 2 diabetes, she continued. The mechanism of these benefits is unclear.

“It’s not known if it’s caffeine or some other constituent of the bean; a phenol, for example. The story behind tea is not as compelling as for coffee, so it may be something beyond caffeine,” according to Dr. Abdelmalek.

Session moderator Norah A. Terrault, MD, MPH, noted that drinking at least two cups of coffee per day has also been associated with reduced risk of cirrhosis in patients with hepatitis B or hepatitis C infection. So she too is on board the coffee express.

“I’m also a big proponent of recommending coffee. We take so much away from the patients, it’s nice to give them back something, right?” said Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.
 

Diet and exercise

Most of the major gastroenterology professional societies emphasize in their practice guidelines for NAFLD that diet and routine physical activity are mandatory. If sustained, these lifestyle modifications can improve NASH and hepatic fibrosis, as well as reduce the risk of portal hypertension and liver cancer. Dr. Abdelmalek counsels her patients to aim for at least 150 minutes per week of moderate or vigorous aerobic and/or resistance exercise. She doesn’t care about the exercise intensity or type, noting that what she considers to be “a beautifully done intervention trial” in 220 patients over the course of 12 months concluded that both moderate and vigorous exercise achieved a significant reduction in intrahepatic triglyceride content.

“Tailor exercise to what patients can do, what they enjoy, and what they can sustain,” she advised.

She identifies and addresses all modifiable risk factors for NAFLD, including hypertension, diabetes, abdominal obesity, smoking, excessive alcohol intake, obstructive sleep apnea, and an unhealthy diet high in fat, red meat, and fructose.

“The primary message I tell my patients interested in dieting is: I want you to find the right approach for you. There is no right or wrong answer. For some of my patients, it’s intermittent fasting and having their first meal at 2 or 3 o’clock in the afternoon. For others it’s a Weight Watchers approach, or a Mediterranean diet, or it’s high protein. The bottom line of my approach is a gravitation away from excess carbohydrates and fats, and beyond that if I can achieve weight loss through caloric restriction or intermittent fasting, I try to tailor that to my patients’ preferences. I do send them to nutritionists,” the gastroenterologist said.

A 7%-10% weight loss has been shown to result in resolution of NASH in 64%-90% of patients. However, only about 10% of patients who achieve clinically meaningful weight loss short term are able to maintain it at 1 year, so ongoing follow-up is essential.

At present there is no FDA-approved therapy for NAFLD/NASH. Beyond diet and exercise – and coffee – there is the option of antiobesity weight-loss drug therapy, which is about as effective as successful lifestyle modification, and bariatric surgery, which is dramatically effective. French surgeons recently reported in a prospective single-center study of 180 severely obese patients with NASH who underwent bariatric surgery that, at 5 years’ follow-up, 84% of them had resolution of NASH with no worsening of liver fibrosis. Indeed, 63% of patients with mild fibrosis at baseline experienced complete resolution of their fibrosis at follow-up, as did 46% of those with more severe baseline bridging fibrosis.

Dr. Abdelmalek reported having no financial conflicts of interest regarding her presentation.

[email protected]

Treatment of obesity through exercise and diet is unquestionably the foundation of care for patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). But drinking at least several cups of coffee a day makes for additional powerful medicine, said Manal F. Abdelmalek, MD, MPH, at the Gastroenterology Updates, IBD, Liver Disease Conference.

s-photo/iStockphoto.com

“I do recommend at least two to three cups of coffee per day for my patients with NAFLD,” said Dr. Abdelmalek, professor of medicine and a gastroenterologist at Duke University, Durham, N.C.

Her thinking on this recommendation has been influenced by a meta-analysis of 16 studies including more than 3,000 coffee drinkers and 132,000 nonconsumers; the meta-analysis concluded that coffee drinkers were 39% less likely to develop cirrhosis. There was evidence of a dose-response effect: Consumers of two or more cups daily had a 47% reduction in the risk of cirrhosis, compared with the nondrinkers, while more modest consumption was associated with a 34% reduction. Moreover, the investigators found that coffee consumption was also associated with a 27% reduction in the likelihood of developing advanced hepatic fibrosis, compared with that of non–coffee drinkers.

“What’s even more provocative is the evidence that coffee decreases risk of hepatocellular carcinoma,” the gastroenterologist said.

She highlighted a U.K. meta-analysis of 18 cohort studies with 2.27 million participants and 2,905 cases, along with 8 case-control studies featuring a collective 1,825 cases and 4,652 controls. The investigators reported that drinking at least two cups of coffee per day was associated with a 35% reduction in the risk of hepatocellular carcinoma independent of a patient’s stage of liver disease or the presence or absence of high alcohol consumption, smoking, obesity, type 2 diabetes, or hepatitis B or C infection.

“This is very impressive data and certainly not something you should ignore,” according to Dr. Abdelmalek.

There is also “fairly strong” data that coffee reduces the risk of developing type 2 diabetes, she continued. The mechanism of these benefits is unclear.

“It’s not known if it’s caffeine or some other constituent of the bean; a phenol, for example. The story behind tea is not as compelling as for coffee, so it may be something beyond caffeine,” according to Dr. Abdelmalek.

Session moderator Norah A. Terrault, MD, MPH, noted that drinking at least two cups of coffee per day has also been associated with reduced risk of cirrhosis in patients with hepatitis B or hepatitis C infection. So she too is on board the coffee express.

“I’m also a big proponent of recommending coffee. We take so much away from the patients, it’s nice to give them back something, right?” said Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.
 

Diet and exercise

Most of the major gastroenterology professional societies emphasize in their practice guidelines for NAFLD that diet and routine physical activity are mandatory. If sustained, these lifestyle modifications can improve NASH and hepatic fibrosis, as well as reduce the risk of portal hypertension and liver cancer. Dr. Abdelmalek counsels her patients to aim for at least 150 minutes per week of moderate or vigorous aerobic and/or resistance exercise. She doesn’t care about the exercise intensity or type, noting that what she considers to be “a beautifully done intervention trial” in 220 patients over the course of 12 months concluded that both moderate and vigorous exercise achieved a significant reduction in intrahepatic triglyceride content.

“Tailor exercise to what patients can do, what they enjoy, and what they can sustain,” she advised.

She identifies and addresses all modifiable risk factors for NAFLD, including hypertension, diabetes, abdominal obesity, smoking, excessive alcohol intake, obstructive sleep apnea, and an unhealthy diet high in fat, red meat, and fructose.

“The primary message I tell my patients interested in dieting is: I want you to find the right approach for you. There is no right or wrong answer. For some of my patients, it’s intermittent fasting and having their first meal at 2 or 3 o’clock in the afternoon. For others it’s a Weight Watchers approach, or a Mediterranean diet, or it’s high protein. The bottom line of my approach is a gravitation away from excess carbohydrates and fats, and beyond that if I can achieve weight loss through caloric restriction or intermittent fasting, I try to tailor that to my patients’ preferences. I do send them to nutritionists,” the gastroenterologist said.

A 7%-10% weight loss has been shown to result in resolution of NASH in 64%-90% of patients. However, only about 10% of patients who achieve clinically meaningful weight loss short term are able to maintain it at 1 year, so ongoing follow-up is essential.

At present there is no FDA-approved therapy for NAFLD/NASH. Beyond diet and exercise – and coffee – there is the option of antiobesity weight-loss drug therapy, which is about as effective as successful lifestyle modification, and bariatric surgery, which is dramatically effective. French surgeons recently reported in a prospective single-center study of 180 severely obese patients with NASH who underwent bariatric surgery that, at 5 years’ follow-up, 84% of them had resolution of NASH with no worsening of liver fibrosis. Indeed, 63% of patients with mild fibrosis at baseline experienced complete resolution of their fibrosis at follow-up, as did 46% of those with more severe baseline bridging fibrosis.

Dr. Abdelmalek reported having no financial conflicts of interest regarding her presentation.

[email protected]

Treatment of obesity through exercise and diet is unquestionably the foundation of care for patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). But drinking at least several cups of coffee a day makes for additional powerful medicine, said Manal F. Abdelmalek, MD, MPH, at the Gastroenterology Updates, IBD, Liver Disease Conference.

s-photo/iStockphoto.com

“I do recommend at least two to three cups of coffee per day for my patients with NAFLD,” said Dr. Abdelmalek, professor of medicine and a gastroenterologist at Duke University, Durham, N.C.

Her thinking on this recommendation has been influenced by a meta-analysis of 16 studies including more than 3,000 coffee drinkers and 132,000 nonconsumers; the meta-analysis concluded that coffee drinkers were 39% less likely to develop cirrhosis. There was evidence of a dose-response effect: Consumers of two or more cups daily had a 47% reduction in the risk of cirrhosis, compared with the nondrinkers, while more modest consumption was associated with a 34% reduction. Moreover, the investigators found that coffee consumption was also associated with a 27% reduction in the likelihood of developing advanced hepatic fibrosis, compared with that of non–coffee drinkers.

“What’s even more provocative is the evidence that coffee decreases risk of hepatocellular carcinoma,” the gastroenterologist said.

She highlighted a U.K. meta-analysis of 18 cohort studies with 2.27 million participants and 2,905 cases, along with 8 case-control studies featuring a collective 1,825 cases and 4,652 controls. The investigators reported that drinking at least two cups of coffee per day was associated with a 35% reduction in the risk of hepatocellular carcinoma independent of a patient’s stage of liver disease or the presence or absence of high alcohol consumption, smoking, obesity, type 2 diabetes, or hepatitis B or C infection.

“This is very impressive data and certainly not something you should ignore,” according to Dr. Abdelmalek.

There is also “fairly strong” data that coffee reduces the risk of developing type 2 diabetes, she continued. The mechanism of these benefits is unclear.

“It’s not known if it’s caffeine or some other constituent of the bean; a phenol, for example. The story behind tea is not as compelling as for coffee, so it may be something beyond caffeine,” according to Dr. Abdelmalek.

Session moderator Norah A. Terrault, MD, MPH, noted that drinking at least two cups of coffee per day has also been associated with reduced risk of cirrhosis in patients with hepatitis B or hepatitis C infection. So she too is on board the coffee express.

“I’m also a big proponent of recommending coffee. We take so much away from the patients, it’s nice to give them back something, right?” said Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.
 

Diet and exercise

Most of the major gastroenterology professional societies emphasize in their practice guidelines for NAFLD that diet and routine physical activity are mandatory. If sustained, these lifestyle modifications can improve NASH and hepatic fibrosis, as well as reduce the risk of portal hypertension and liver cancer. Dr. Abdelmalek counsels her patients to aim for at least 150 minutes per week of moderate or vigorous aerobic and/or resistance exercise. She doesn’t care about the exercise intensity or type, noting that what she considers to be “a beautifully done intervention trial” in 220 patients over the course of 12 months concluded that both moderate and vigorous exercise achieved a significant reduction in intrahepatic triglyceride content.

“Tailor exercise to what patients can do, what they enjoy, and what they can sustain,” she advised.

She identifies and addresses all modifiable risk factors for NAFLD, including hypertension, diabetes, abdominal obesity, smoking, excessive alcohol intake, obstructive sleep apnea, and an unhealthy diet high in fat, red meat, and fructose.

“The primary message I tell my patients interested in dieting is: I want you to find the right approach for you. There is no right or wrong answer. For some of my patients, it’s intermittent fasting and having their first meal at 2 or 3 o’clock in the afternoon. For others it’s a Weight Watchers approach, or a Mediterranean diet, or it’s high protein. The bottom line of my approach is a gravitation away from excess carbohydrates and fats, and beyond that if I can achieve weight loss through caloric restriction or intermittent fasting, I try to tailor that to my patients’ preferences. I do send them to nutritionists,” the gastroenterologist said.

A 7%-10% weight loss has been shown to result in resolution of NASH in 64%-90% of patients. However, only about 10% of patients who achieve clinically meaningful weight loss short term are able to maintain it at 1 year, so ongoing follow-up is essential.

At present there is no FDA-approved therapy for NAFLD/NASH. Beyond diet and exercise – and coffee – there is the option of antiobesity weight-loss drug therapy, which is about as effective as successful lifestyle modification, and bariatric surgery, which is dramatically effective. French surgeons recently reported in a prospective single-center study of 180 severely obese patients with NASH who underwent bariatric surgery that, at 5 years’ follow-up, 84% of them had resolution of NASH with no worsening of liver fibrosis. Indeed, 63% of patients with mild fibrosis at baseline experienced complete resolution of their fibrosis at follow-up, as did 46% of those with more severe baseline bridging fibrosis.

Dr. Abdelmalek reported having no financial conflicts of interest regarding her presentation.

[email protected]

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

A version of this article first appeared on Medscape.com.

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

A version of this article first appeared on Medscape.com.

Six pregnancy-related complications increase a woman’s risk of developing risk factors for cardiovascular disease (CVD) and subsequently developing CVD, the American Heart Association says in a new scientific statement.

They are hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age (SGA) delivery, placental abruption (abruptio placentae), and pregnancy loss.

A history of any of these adverse pregnancy outcomes should prompt “more vigorous primordial prevention of CVD risk factors and primary prevention of CVD,” the writing group says.

“Adverse pregnancy outcomes are linked to women having hypertension, diabetes, abnormal cholesterol, and cardiovascular disease events, including heart attack and stroke, long after their pregnancies,” Nisha I. Parikh, MD, MPH, chair of the writing group, said in a news release.

Adverse pregnancy outcomes can be a “powerful window” into CVD prevention “if women and their health care professionals harness the knowledge and use it for health improvement,” said Dr. Parikh, associate professor of medicine in the cardiovascular division at the University of California, San Francisco.

The statement was published online March 29 in Circulation.

For the scientific statement, the writing group reviewed the latest scientific literature on adverse pregnancy outcomes and CVD risk. 

The evidence in the literature linking adverse pregnancy outcomes to later CVD is “consistent over many years and confirmed in nearly every study we examined,” Dr. Parikh said. Among their key findings:

• Gestational hypertension is associated with an increased risk of CVD later in life by 67% and the odds of stroke by 83%. Moderate and severe  is associated with a more than twofold increase in the risk for CVD.
• Gestational diabetes is associated with an increase in the risk for CVD by 68% and the risk of developing  after pregnancy by 10-fold.
• Preterm delivery (before 37 weeks) is associated with double the risk of developing CVD and is strongly associated with later heart disease, stroke, and CVD.
• Placental abruption is associated with an 82% increased risk for CVD.
• Stillbirth is associated with about double the risk for CVD.

“This statement should inform future prevention guidelines in terms of the important factors to consider for determining women’s risk for heart diseases and stroke,” Dr. Parikh added.

The statement emphasizes the importance of recognizing these adverse pregnancy outcomes when evaluating CVD risk in women but notes that their value in reclassifying CVD risk may not be established.

It highlights the importance of adopting a heart-healthy diet and increasing physical activity among women with any of these pregnancy-related complications, starting right after childbirth and continuing across the life span to decrease CVD risk.

Lactation and breastfeeding may lower a woman’s later cardiometabolic risk, the writing group notes.
 

‘Golden year of opportunity’

The statement highlights several opportunities to improve transition of care for women with adverse pregnancy outcomes and to implement strategies to reduce their long-term CVD risk.

One strategy is longer postpartum follow-up care, sometimes referred to as the “fourth trimester,” to screen for CVD risk factors and provide CVD prevention counseling.

Another strategy involves improving the transfer of health information between ob/gyns and primary care physicians to eliminate inconsistencies in electronic health record documentation, which should improve patient care.

A third strategy is obtaining a short and targeted health history for each woman to confirm if she has any of the six pregnancy-related complications.

“If a woman has had any of these adverse pregnancy outcomes, consider close blood pressure monitoring, type 2 diabetes and lipid screening, and more aggressive risk factor modification and CVD prevention recommendations,” Dr. Parikh advised.

“Our data [lend] support to the prior AHA recommendation that these important adverse pregnancy outcomes should be ‘risk enhancers’ to guide consideration for statin therapy aimed at CVD prevention in women,” Dr. Parikh added.

In a commentary in Circulation, Eliza C. Miller, MD, assistant professor of neurology at Columbia University, New York, notes that pregnancy and the postpartum period are a critical time window in a woman’s life to identify CVD risk and improve a woman’s health trajectory.

“The so-called ‘Golden Hour’ for conditions such as sepsis and acute stroke refers to a critical time window for early recognition and treatment, when we can change a patient’s clinical trajectory and prevent severe morbidity and mortality,” writes Dr. Miller.

“Pregnancy and the postpartum period can be considered a ‘Golden Year’ in a woman’s life, offering a rare opportunity for clinicians to identify young women at risk and work with them to improve their cardiovascular health trajectories,” she notes.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Stroke Council.

The authors of the scientific statement have disclosed no relevant financial relationships. Dr. Miller received personal compensation from Finch McCranie and Argionis & Associates for expert testimony regarding maternal stroke; and personal compensation from Elsevier for editorial work on Handbook of Clinical Neurology, Vol. 171 and 172 (Neurology of Pregnancy).

A version of this article first appeared on Medscape.com.

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

A version of this article first appeared on Medscape.com.

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

A version of this article first appeared on Medscape.com.

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

A version of this article first appeared on Medscape.com.

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]