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Abaloparatide works in ‘ignored population’: Men with osteoporosis
San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.
Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.
Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.
“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.
Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.
While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.
About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.
Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
Screen men with hypogonadism or those taking steroids
“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.
Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.
Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.
But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”
ATOM Study: Significant BMD increases at key sites
The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).
The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.
Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).
Three fractures occurred in those receiving placebo and one with abaloparatide.
For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).
The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.
Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).
A version of this article first appeared on Medscape.com.
San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.
Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.
Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.
“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.
Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.
While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.
About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.
Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
Screen men with hypogonadism or those taking steroids
“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.
Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.
Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.
But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”
ATOM Study: Significant BMD increases at key sites
The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).
The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.
Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).
Three fractures occurred in those receiving placebo and one with abaloparatide.
For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).
The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.
Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).
A version of this article first appeared on Medscape.com.
San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.
Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.
Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.
“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.
Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.
While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.
About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.
Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
Screen men with hypogonadism or those taking steroids
“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.
Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.
Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.
But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”
ATOM Study: Significant BMD increases at key sites
The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).
The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.
Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).
Three fractures occurred in those receiving placebo and one with abaloparatide.
For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).
The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.
Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).
A version of this article first appeared on Medscape.com.
AT AACE 2022
First fatty liver guidelines for endocrinology, primary care
New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.
They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.
The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.
These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.
80 million Americans have NAFLD, but very few are aware
The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.
The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.
Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.
In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.
In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”
And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
Screening advised using new FIB-4 test
The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).
The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).
Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.
“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.
The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.
For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.
Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.
“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
NAFLD treatment in endocrinology and primary care: CVD prevention
During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.
Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.
There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.
The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.
In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”
To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”
Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.
A version of this article first appeared on Medscape.com.
New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.
They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.
The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.
These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.
80 million Americans have NAFLD, but very few are aware
The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.
The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.
Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.
In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.
In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”
And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
Screening advised using new FIB-4 test
The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).
The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).
Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.
“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.
The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.
For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.
Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.
“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
NAFLD treatment in endocrinology and primary care: CVD prevention
During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.
Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.
There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.
The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.
In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”
To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”
Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.
A version of this article first appeared on Medscape.com.
New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.
They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.
The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.
These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.
80 million Americans have NAFLD, but very few are aware
The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.
The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.
Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.
In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.
In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”
And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
Screening advised using new FIB-4 test
The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).
The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (109/L) x ALT ½ (U/L).
Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.
“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.
The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.
For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.
Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.
“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
NAFLD treatment in endocrinology and primary care: CVD prevention
During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.
Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.
There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.
The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.
In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”
To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”
Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.
A version of this article first appeared on Medscape.com.
FROM AACE 2022