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One in three older adults with epilepsy has poor adherence to antiepileptics
HOUSTON – One in three older Americans with epilepsy had poor adherence to antiepileptic drugs, according to a large retrospective study, and the numbers were even worse for members of minority populations.
In an analysis of Medicare claims, patients who were African American had an odds ratio of 1.56 (95% confidence interval, 1.46-1.68) for being non-adherent to antiepileptic drugs (AEDs). For Hispanic patients, the OR was 1.40 (95% CI, 1.28-1.54), while for Asians, the OR was 1.41 (95% CI, 1.25-1.54).
“Overall, 31.8% were non-adherent to AEDs; range was from 24.1% for whites to 34.3% for African Americans,” wrote Maria Pisu, PhD, and her collaborators in an abstract accompanying the poster presented at the annual meeting of the American Epilepsy Society.
The reasons for poor adherence are unknown, but warrant further investigation, said Dr. Pisu of the division of preventive medicine at the University of Alabama at Birmingham.
The sample included 36,912 patients with epilepsy. In the enhanced sample, 19.2% of patients were white, 62.5% were African American, 11.3% were Hispanic, 5.0% were Asian, and 2.0% were American Indian or Alaskan Native. Of the sample, 61.6% were female; 41.5% of patients were aged 66-74 years; 36.1% were aged 75-84 years; and 22.4% were 85 years or older.
In order to determine whether patients with epilepsy or seizures were adherent, investigators looked at the ratio of days that at least one AED prescription was in the database for a given patient, divided by the total days of follow-up on record (“proportion of days covered”). The primary outcome measure of nonadherence was defined as a proportion of days covered of less than 0.80.
Most patients had one to several comorbidities: only 8.3% had no other comorbidities, while 46.0% had more than four. The remainder fell somewhere in the middle.
A majority of patients (59.2%) had some form of copay or coinsurance for prescriptions. About half of patients (50.2%) lived in the South.
Through multivariable analysis, the investigators explored the relationships between nonadherence and race or ethnicity, demographics, geographic area of residence, comorbidities, and whether the prescribed AEDs were enzyme-inducing. Additionally, socioeconomic status was estimated by factoring in eligibility for Medicare Part D low income subsidies and using zip code–level poverty data.
The differences between ethnic groups, wrote Dr. Pisu, were significant “after accounting for several factors that affect prescription-taking factors, e.g., economic constraints,” so it was not just low socioeconomic status that accounted for the discrepancy.
The retrospective claims-based study was limited by several factors, wrote Dr. Pisu and her colleagues. True adherence is difficult to quantify, and may be overestimated by measuring filled prescriptions; on the other hand, some patients may have had other insurance coverage, and obtained medication through a means not captured in the study. Finally, dose adjustments may mean patients can “stretch” medications, thereby remaining adherent without refilling prescriptions.
Still, the study shows that nonadherence is pervasive among older Americans with epilepsy, with worse adherence among members of minority populations. “Interventions to promote adherence are important. These should account for the impact of drug cost-sharing and socioeconomic status on epilepsy treatment,” wrote Dr. Pisu.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Pisu reported no relevant financial disclosures.
[email protected]
On Twitter @karioakes
HOUSTON – One in three older Americans with epilepsy had poor adherence to antiepileptic drugs, according to a large retrospective study, and the numbers were even worse for members of minority populations.
In an analysis of Medicare claims, patients who were African American had an odds ratio of 1.56 (95% confidence interval, 1.46-1.68) for being non-adherent to antiepileptic drugs (AEDs). For Hispanic patients, the OR was 1.40 (95% CI, 1.28-1.54), while for Asians, the OR was 1.41 (95% CI, 1.25-1.54).
“Overall, 31.8% were non-adherent to AEDs; range was from 24.1% for whites to 34.3% for African Americans,” wrote Maria Pisu, PhD, and her collaborators in an abstract accompanying the poster presented at the annual meeting of the American Epilepsy Society.
The reasons for poor adherence are unknown, but warrant further investigation, said Dr. Pisu of the division of preventive medicine at the University of Alabama at Birmingham.
The sample included 36,912 patients with epilepsy. In the enhanced sample, 19.2% of patients were white, 62.5% were African American, 11.3% were Hispanic, 5.0% were Asian, and 2.0% were American Indian or Alaskan Native. Of the sample, 61.6% were female; 41.5% of patients were aged 66-74 years; 36.1% were aged 75-84 years; and 22.4% were 85 years or older.
In order to determine whether patients with epilepsy or seizures were adherent, investigators looked at the ratio of days that at least one AED prescription was in the database for a given patient, divided by the total days of follow-up on record (“proportion of days covered”). The primary outcome measure of nonadherence was defined as a proportion of days covered of less than 0.80.
Most patients had one to several comorbidities: only 8.3% had no other comorbidities, while 46.0% had more than four. The remainder fell somewhere in the middle.
A majority of patients (59.2%) had some form of copay or coinsurance for prescriptions. About half of patients (50.2%) lived in the South.
Through multivariable analysis, the investigators explored the relationships between nonadherence and race or ethnicity, demographics, geographic area of residence, comorbidities, and whether the prescribed AEDs were enzyme-inducing. Additionally, socioeconomic status was estimated by factoring in eligibility for Medicare Part D low income subsidies and using zip code–level poverty data.
The differences between ethnic groups, wrote Dr. Pisu, were significant “after accounting for several factors that affect prescription-taking factors, e.g., economic constraints,” so it was not just low socioeconomic status that accounted for the discrepancy.
The retrospective claims-based study was limited by several factors, wrote Dr. Pisu and her colleagues. True adherence is difficult to quantify, and may be overestimated by measuring filled prescriptions; on the other hand, some patients may have had other insurance coverage, and obtained medication through a means not captured in the study. Finally, dose adjustments may mean patients can “stretch” medications, thereby remaining adherent without refilling prescriptions.
Still, the study shows that nonadherence is pervasive among older Americans with epilepsy, with worse adherence among members of minority populations. “Interventions to promote adherence are important. These should account for the impact of drug cost-sharing and socioeconomic status on epilepsy treatment,” wrote Dr. Pisu.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Pisu reported no relevant financial disclosures.
[email protected]
On Twitter @karioakes
HOUSTON – One in three older Americans with epilepsy had poor adherence to antiepileptic drugs, according to a large retrospective study, and the numbers were even worse for members of minority populations.
In an analysis of Medicare claims, patients who were African American had an odds ratio of 1.56 (95% confidence interval, 1.46-1.68) for being non-adherent to antiepileptic drugs (AEDs). For Hispanic patients, the OR was 1.40 (95% CI, 1.28-1.54), while for Asians, the OR was 1.41 (95% CI, 1.25-1.54).
“Overall, 31.8% were non-adherent to AEDs; range was from 24.1% for whites to 34.3% for African Americans,” wrote Maria Pisu, PhD, and her collaborators in an abstract accompanying the poster presented at the annual meeting of the American Epilepsy Society.
The reasons for poor adherence are unknown, but warrant further investigation, said Dr. Pisu of the division of preventive medicine at the University of Alabama at Birmingham.
The sample included 36,912 patients with epilepsy. In the enhanced sample, 19.2% of patients were white, 62.5% were African American, 11.3% were Hispanic, 5.0% were Asian, and 2.0% were American Indian or Alaskan Native. Of the sample, 61.6% were female; 41.5% of patients were aged 66-74 years; 36.1% were aged 75-84 years; and 22.4% were 85 years or older.
In order to determine whether patients with epilepsy or seizures were adherent, investigators looked at the ratio of days that at least one AED prescription was in the database for a given patient, divided by the total days of follow-up on record (“proportion of days covered”). The primary outcome measure of nonadherence was defined as a proportion of days covered of less than 0.80.
Most patients had one to several comorbidities: only 8.3% had no other comorbidities, while 46.0% had more than four. The remainder fell somewhere in the middle.
A majority of patients (59.2%) had some form of copay or coinsurance for prescriptions. About half of patients (50.2%) lived in the South.
Through multivariable analysis, the investigators explored the relationships between nonadherence and race or ethnicity, demographics, geographic area of residence, comorbidities, and whether the prescribed AEDs were enzyme-inducing. Additionally, socioeconomic status was estimated by factoring in eligibility for Medicare Part D low income subsidies and using zip code–level poverty data.
The differences between ethnic groups, wrote Dr. Pisu, were significant “after accounting for several factors that affect prescription-taking factors, e.g., economic constraints,” so it was not just low socioeconomic status that accounted for the discrepancy.
The retrospective claims-based study was limited by several factors, wrote Dr. Pisu and her colleagues. True adherence is difficult to quantify, and may be overestimated by measuring filled prescriptions; on the other hand, some patients may have had other insurance coverage, and obtained medication through a means not captured in the study. Finally, dose adjustments may mean patients can “stretch” medications, thereby remaining adherent without refilling prescriptions.
Still, the study shows that nonadherence is pervasive among older Americans with epilepsy, with worse adherence among members of minority populations. “Interventions to promote adherence are important. These should account for the impact of drug cost-sharing and socioeconomic status on epilepsy treatment,” wrote Dr. Pisu.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Pisu reported no relevant financial disclosures.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: For African-American patients, the odds ratio was 1.56 for being nonadherent (95% CI, 1.4-1.68).
Data source: Retrospective analysis of Medicare administrative claims data from 2008 to 2010, examining a 5% sample of patients with epilepsy aged 66 and over, and including all members of racial/ethnic minority populations who had claims for diagnoses of seizures or epilepsy.
Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Pisu reported no relevant financial disclosures.
Ketogenic diet, with variations, can help adult epilepsy
HOUSTON – The ketogenic diet is usually thought of as a solution of near-last resort for pediatric epilepsy, but some adolescents and adults with epilepsy can also benefit from a very low carbohydrate diet.
There are also limited data to suggest that more palatable adaptations of the diet may provide benefit while improving adherence, said Mackenzie C. Cervenka, MD, speaking at the annual meeting of the American Epilepsy Society.
“Ketogenic diets are a reasonable option for older adolescents and adults with drug-resistant epilepsy that’s not amenable to surgical intervention,” said Dr. Cervenka, director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore.
The antiepileptic benefit of a diet that induces ketogenesis, forcing the brain to utilize ketone bodies rather than glucose for energy, has been known since the 1920s, with benefit seen for adolescents and adults in studies completed in the 1930s. These diets mimic a starvation state, but provide enough calories through fat or protein to maintain weight. Calories in the traditional ketogenic diet, Dr. Cervenka said, are about 90% fat. Food for patients on this diet should be weighed on a gram scale, and those preparing meals should aim for a ratio of 3 to 4 grams of fat for each gram of carbohydrate and protein combined. A modified version uses a 1:1 or 2:1 ratio, a more appealing configuration for some patients.
Weighing each bite of food is cumbersome, and palatability can be a major problem as well, contributing to adherence problems with such a high-fat diet. However, for patients who are so ill that they are tube-fed, commercially available ketogenic formulas are available. Necessary supplementation on a traditional ketogenic diet includes calcium, vitamin D, multivitamins, and oral citrates to prevent kidney stone formation, she said.
However, ketogenic diets are known to be anti-inflammatory: Animal models have shown less inflammation, pain, and fever when rats are fed a ketogenic diet. Also, proinflammatory cytokines and chemokines are reduced on a ketogenic diet in a rodent model of Parkinson’s disease and multiple sclerosis. Particularly for patients with autoimmune encephalopathies, the ketogenic diet has been shown to be of benefit.
One option with promising, but limited, results is a low-carbohydrate diet rich in medium-chain triglycerides. Medium chain triglyceride (MCT) oil is available in a commercial preparation derived from coconut or palm kernel oil. On this diet, 30%-60% of calories should come from MCTs, which is usually sufficient to induce ketosis. However, gastrointestinal side effects such as bloating and diarrhea can be pronounced, especially if the diet is begun abruptly. It’s best to ramp up slowly with MCTs, so this diet would not be appropriate for the patient who needs quick improvement in seizure control, Dr. Cervenka said.
A modified Atkins diet provides 15-20 grams of net carbohydrates daily, after dietary fiber is subtracted. Using this strategy, adolescents and adults don’t have to weigh foods. Rather, food tables are used to track carbohydrates and fiber, and ketosis is assessed by measuring urine ketones on a test strip. The goal, Dr. Cervenka said, is to achieve moderate to large ketosis (40-160 ng/mL urine ketones).
Finally, low glycemic index treatment (LGIT) is an option worth considering. This diet takes advantage of certain carbohydrate-rich foods that do not raise blood sugar quickly, such as fiber-rich vegetables or legumes with some fat content. Patients on the LGIT diet can have from 40 to 60 grams of carbohydrate daily, and the diet has been used with some success in drug-resistant childhood epilepsy as well as Angelman syndrome, she said.
Though sample sizes are small and efficacy may be modest, Dr. Cervenka said, “the effect is quick.” Finding less-restrictive modifications of these diets may help patients stay on the diet over the long term, increasing real-world effectiveness.
But long-term adherence to a ketogenic or other high-fat, low-residue diet comes with a host of unknowns about cardiovascular, metabolic, and renal health; ongoing study of these patients may yield answers about whether theoretical concerns are borne out, and whether the risk is worth it in terms of seizure benefit.
Dr. Cervenka reported receiving grant support from Nutricia North America, Vitaflo, and the BrightFocus Foundation. She has also received an honorarium for speaking from LivaNova.
[email protected]
On Twitter @karioakes
HOUSTON – The ketogenic diet is usually thought of as a solution of near-last resort for pediatric epilepsy, but some adolescents and adults with epilepsy can also benefit from a very low carbohydrate diet.
There are also limited data to suggest that more palatable adaptations of the diet may provide benefit while improving adherence, said Mackenzie C. Cervenka, MD, speaking at the annual meeting of the American Epilepsy Society.
“Ketogenic diets are a reasonable option for older adolescents and adults with drug-resistant epilepsy that’s not amenable to surgical intervention,” said Dr. Cervenka, director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore.
The antiepileptic benefit of a diet that induces ketogenesis, forcing the brain to utilize ketone bodies rather than glucose for energy, has been known since the 1920s, with benefit seen for adolescents and adults in studies completed in the 1930s. These diets mimic a starvation state, but provide enough calories through fat or protein to maintain weight. Calories in the traditional ketogenic diet, Dr. Cervenka said, are about 90% fat. Food for patients on this diet should be weighed on a gram scale, and those preparing meals should aim for a ratio of 3 to 4 grams of fat for each gram of carbohydrate and protein combined. A modified version uses a 1:1 or 2:1 ratio, a more appealing configuration for some patients.
Weighing each bite of food is cumbersome, and palatability can be a major problem as well, contributing to adherence problems with such a high-fat diet. However, for patients who are so ill that they are tube-fed, commercially available ketogenic formulas are available. Necessary supplementation on a traditional ketogenic diet includes calcium, vitamin D, multivitamins, and oral citrates to prevent kidney stone formation, she said.
However, ketogenic diets are known to be anti-inflammatory: Animal models have shown less inflammation, pain, and fever when rats are fed a ketogenic diet. Also, proinflammatory cytokines and chemokines are reduced on a ketogenic diet in a rodent model of Parkinson’s disease and multiple sclerosis. Particularly for patients with autoimmune encephalopathies, the ketogenic diet has been shown to be of benefit.
One option with promising, but limited, results is a low-carbohydrate diet rich in medium-chain triglycerides. Medium chain triglyceride (MCT) oil is available in a commercial preparation derived from coconut or palm kernel oil. On this diet, 30%-60% of calories should come from MCTs, which is usually sufficient to induce ketosis. However, gastrointestinal side effects such as bloating and diarrhea can be pronounced, especially if the diet is begun abruptly. It’s best to ramp up slowly with MCTs, so this diet would not be appropriate for the patient who needs quick improvement in seizure control, Dr. Cervenka said.
A modified Atkins diet provides 15-20 grams of net carbohydrates daily, after dietary fiber is subtracted. Using this strategy, adolescents and adults don’t have to weigh foods. Rather, food tables are used to track carbohydrates and fiber, and ketosis is assessed by measuring urine ketones on a test strip. The goal, Dr. Cervenka said, is to achieve moderate to large ketosis (40-160 ng/mL urine ketones).
Finally, low glycemic index treatment (LGIT) is an option worth considering. This diet takes advantage of certain carbohydrate-rich foods that do not raise blood sugar quickly, such as fiber-rich vegetables or legumes with some fat content. Patients on the LGIT diet can have from 40 to 60 grams of carbohydrate daily, and the diet has been used with some success in drug-resistant childhood epilepsy as well as Angelman syndrome, she said.
Though sample sizes are small and efficacy may be modest, Dr. Cervenka said, “the effect is quick.” Finding less-restrictive modifications of these diets may help patients stay on the diet over the long term, increasing real-world effectiveness.
But long-term adherence to a ketogenic or other high-fat, low-residue diet comes with a host of unknowns about cardiovascular, metabolic, and renal health; ongoing study of these patients may yield answers about whether theoretical concerns are borne out, and whether the risk is worth it in terms of seizure benefit.
Dr. Cervenka reported receiving grant support from Nutricia North America, Vitaflo, and the BrightFocus Foundation. She has also received an honorarium for speaking from LivaNova.
[email protected]
On Twitter @karioakes
HOUSTON – The ketogenic diet is usually thought of as a solution of near-last resort for pediatric epilepsy, but some adolescents and adults with epilepsy can also benefit from a very low carbohydrate diet.
There are also limited data to suggest that more palatable adaptations of the diet may provide benefit while improving adherence, said Mackenzie C. Cervenka, MD, speaking at the annual meeting of the American Epilepsy Society.
“Ketogenic diets are a reasonable option for older adolescents and adults with drug-resistant epilepsy that’s not amenable to surgical intervention,” said Dr. Cervenka, director of the Adult Epilepsy Diet Center at Johns Hopkins University, Baltimore.
The antiepileptic benefit of a diet that induces ketogenesis, forcing the brain to utilize ketone bodies rather than glucose for energy, has been known since the 1920s, with benefit seen for adolescents and adults in studies completed in the 1930s. These diets mimic a starvation state, but provide enough calories through fat or protein to maintain weight. Calories in the traditional ketogenic diet, Dr. Cervenka said, are about 90% fat. Food for patients on this diet should be weighed on a gram scale, and those preparing meals should aim for a ratio of 3 to 4 grams of fat for each gram of carbohydrate and protein combined. A modified version uses a 1:1 or 2:1 ratio, a more appealing configuration for some patients.
Weighing each bite of food is cumbersome, and palatability can be a major problem as well, contributing to adherence problems with such a high-fat diet. However, for patients who are so ill that they are tube-fed, commercially available ketogenic formulas are available. Necessary supplementation on a traditional ketogenic diet includes calcium, vitamin D, multivitamins, and oral citrates to prevent kidney stone formation, she said.
However, ketogenic diets are known to be anti-inflammatory: Animal models have shown less inflammation, pain, and fever when rats are fed a ketogenic diet. Also, proinflammatory cytokines and chemokines are reduced on a ketogenic diet in a rodent model of Parkinson’s disease and multiple sclerosis. Particularly for patients with autoimmune encephalopathies, the ketogenic diet has been shown to be of benefit.
One option with promising, but limited, results is a low-carbohydrate diet rich in medium-chain triglycerides. Medium chain triglyceride (MCT) oil is available in a commercial preparation derived from coconut or palm kernel oil. On this diet, 30%-60% of calories should come from MCTs, which is usually sufficient to induce ketosis. However, gastrointestinal side effects such as bloating and diarrhea can be pronounced, especially if the diet is begun abruptly. It’s best to ramp up slowly with MCTs, so this diet would not be appropriate for the patient who needs quick improvement in seizure control, Dr. Cervenka said.
A modified Atkins diet provides 15-20 grams of net carbohydrates daily, after dietary fiber is subtracted. Using this strategy, adolescents and adults don’t have to weigh foods. Rather, food tables are used to track carbohydrates and fiber, and ketosis is assessed by measuring urine ketones on a test strip. The goal, Dr. Cervenka said, is to achieve moderate to large ketosis (40-160 ng/mL urine ketones).
Finally, low glycemic index treatment (LGIT) is an option worth considering. This diet takes advantage of certain carbohydrate-rich foods that do not raise blood sugar quickly, such as fiber-rich vegetables or legumes with some fat content. Patients on the LGIT diet can have from 40 to 60 grams of carbohydrate daily, and the diet has been used with some success in drug-resistant childhood epilepsy as well as Angelman syndrome, she said.
Though sample sizes are small and efficacy may be modest, Dr. Cervenka said, “the effect is quick.” Finding less-restrictive modifications of these diets may help patients stay on the diet over the long term, increasing real-world effectiveness.
But long-term adherence to a ketogenic or other high-fat, low-residue diet comes with a host of unknowns about cardiovascular, metabolic, and renal health; ongoing study of these patients may yield answers about whether theoretical concerns are borne out, and whether the risk is worth it in terms of seizure benefit.
Dr. Cervenka reported receiving grant support from Nutricia North America, Vitaflo, and the BrightFocus Foundation. She has also received an honorarium for speaking from LivaNova.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM AES 2016
VIDEO: Hepato-adrenal syndrome is an under-recognized source of ICU morbidity
BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.
According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).
Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.
The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.
Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.
Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.
“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.
Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.
[email protected]
On Twitter @karioakes
BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.
According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).
Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.
The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.
Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.
Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.
“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.
Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.
[email protected]
On Twitter @karioakes
BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.
According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).
Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.
The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.
Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.
Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.
“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.
Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.
[email protected]
On Twitter @karioakes
AT THE LIVER MEETING 2016
Key clinical point:
Major finding: Patients with HAS had a longer length of hospital stay (median 29 days, HAS; 17 days, non-HAS; P = .001)
Data source: Single-center study of 69 consecutively enrolled ICU patients with serious liver disease and random cortisol or adrenocorticotropin-releasing hormone results.
Disclosures: The study investigators reported no disclosures, and no external sources of funding.
VIDEO: Appealing DAA denials is worth it for hepatitis C patients
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
AT THE LIVER MEETING 2016
Risk stratification important for aortic valve disease in pregnancy
CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.
Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.
When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).
The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.
WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.
If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.
Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.
“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”
In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.
In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.
Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.
Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.
Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.
The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.
However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.
For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.
Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.
The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.
Dr. O’Gara reported no relevant disclosures.
[email protected]
On Twitter @karioakes
CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.
Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.
When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).
The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.
WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.
If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.
Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.
“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”
In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.
In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.
Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.
Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.
Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.
The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.
However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.
For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.
Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.
The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.
Dr. O’Gara reported no relevant disclosures.
[email protected]
On Twitter @karioakes
CHICAGO – Pregnancy-associated hemodynamic and physiologic changes can challenge hearts with diseased aortic valves. Understanding pregnancy’s toll on the body can help physicians take better care of pregnant women with aortic stenosis or aortic regurgitation, said Patrick T. O’Gara, MD. “This is a relatively infrequent condition, and it causes all of us a great deal of apprehension,” he said.
Dr. O’Gara, director of clinical cardiology at Brigham and Women’s Hospital, Boston, walked attendees through current recommendations for caring for pregnant women with aortic valve disease in a presentation at the annual Heart Valve Summit.
When talking to women with aortic valve disease, it’s important to let them know that a pregnancy during which they experience an adverse maternal cardiac event appears to increase their risk for later events as well, said Dr. O’Gara. One study of pregnancy in women with aortic valve disease, said Dr. O’Gara, found that the risk of later events for women who had had a cardiac event in pregnancy was 27% plus or minus 9 percentage points in the 5 years following pregnancy, while the risk was just 15% plus or minus 3 percentage points for women whose pregnancies were not complicated by cardiac adverse events (P = .02) (Heart. 2010 Oct;96(20):1656-61).
The World Health Organization classification of pregnancy risk, said Dr. O’Gara, provides some guidance. Patients who are WHO class III are considered to be high risk; pregnancy in these individuals calls for counseling and a multidisciplinary care team. Patients who fall into this class are those with mechanical heart valves, those with Marfan syndrome and aortic involvement with a valve diameter of 40-45 mm, and those with bicuspid aortic valve disease with a valve diameter of 45-50 mm.
WHO class IV patients, according to the guidelines, are at prohibitive risk. These patients should consider terminating a pregnancy if one occurs. Conditions that place women into WHO class IV include symptomatic severe aortic stenosis (AS), severe left ventricular dysfunction with an ejection fraction less than 40%, and severe coarctation of the aorta. Women with Marfan syndrome with aortic valve diameters greater than 45 mm and women with bicuspid aortic valves and a diameter over 50 mm also fall into this category of prohibitive risk.
If a physician is lucky enough to have a pre-conception relationship with a patient, then a host of considerations can come into play. In addition to cardiac risk stratification, obstetric and intrapartum risk to the mother as well as neonatal risk should be considered. Some factors to take into account are maternal life expectancy and potential long-term complications to the mother from pregnancy and childbirth.
Plasma volume increases rapidly through the first trimester, plateauing about halfway through pregnancy. With this normal dilutional anemia, “Most normal pregnancies are accompanied by a grade II systolic murmur, best heard at the upper left sternal border,” said Dr. O’Gara. Since stroke volume and heart rate both also increase through pregnancy, cardiac output goes up as well.
“Importantly, systemic vascular resistance is reduced throughout pregnancy,” said Dr. O’Gara. Consequently, “regurgitant heart valve problems are generally much better tolerated than stenotic lesions in pregnancy. That’s physiologic principle number one.”
In labor, abrupt hemodynamic changes include increases in cardiac output, heart rate, blood pressure, and venous return. “Labor and delivery are very stressful hemodynamic times for women,” said Dr. O’Gara.
In the immediate postpartum period, uterine contraction results in a return of a significant amount of blood to the maternal circulation. This effectively creates an autotransfusion, with resulting increased preload and cardiac output. The inferior vena cava is also freed from the pressure of a gravid uterus, increasing venous return further. Finally, there’s also a marked increase in systemic vascular resistance.
Aside from the risk of adverse cardiac events, other adverse outcomes for women can include an increased risk of premature rupture of membranes and postpartum hemorrhage. For the neonate, preterm birth and respiratory distress are more likely. Newborns are more likely to be small for gestational age, to suffer intraventricular hemorrhage, and to die. Depending on the parental genetic status, the infant may be at risk of congenital heart disease as well.
Neonatal risk may also be increased, said Dr. O’Gara. Some maternal conditions that can increase risk for the infant include a baseline New York Heart Association (NYHA) class of greater than II or having cyanosis; having a left heart obstruction; being a smoker; having a multiple gestation; having a mechanical heart valve; and taking an oral anticoagulant.
Ideally, a full discussion would include a genetic referral if indicated, as well as coordination with a gynecologist or primary care provider to provide contraception and to assist with planning for and optimizing outcomes of a pregnancy.
The American College of Cardiology and the American Heart Association have issued guidelines that include a class I recommendation regarding valve intervention before pregnancy for symptomatic patients with severe AS (those with aortic velocity of at least 4.0 m/sec, or mean pressure gradient greater than 41 mm Hg; stage D). For patients who meet the same hemodynamic criteria for severe AS but who are asymptomatic (stage C), the guidelines have a class IIa recommendation that pre-pregnancy valve intervention is “reasonable.” These recommendations have level C evidence supporting them.
However, another class IIa recommendation for patients with severe AS who are already pregnant advises valve intervention only in the case of hemodynamic deterioration, or the development of NYHA class III to IV heart failure symptoms. This is backed by grade B evidence, according to the associations.
For aortic regurgitation (AR), a level I recommendation advises valve repair or replacement before pregnancy if patients are symptomatic and have severe (stage D) regurgitation. Pregnant patients with severe regurgitation should only be considered for a valve operation if they have refractory NYHA class IV heart failure symptoms. These recommendations have level C evidence supporting them.
Since AR is better tolerated in pregnancy than AS, the nature of the valve disease is one of many factors to consider when deciding whether to perform intervention before the patient becomes pregnant. Plans for future pregnancy may also affect the choice of prosthesis, as anticoagulation management during pregnancy can be extremely tricky.
The recommendations overall make clear that, based on available evidence, “there should be a high threshold for intervention during pregnancy,” said Dr. O’Gara. And no one should go it alone when taking care of these complicated patients. “Care of pregnant women with heart disease requires coordination with a multidisciplinary team,” he said.
Dr. O’Gara reported no relevant disclosures.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM THE HEART VALVE SUMMIT
VIDEO: PBC patients with compensated cirrhosis fare well on obeticholic acid
BOSTON – Patients with primary biliary cholangitis (PBC) who have compensated cirrhosis fared just as well on obeticholic acid (OCA) as did PBC patients without cirrhosis, according to an analysis of data from POISE, the pivotal clinical trial for approval of OCA for PBC.
The POISE trial included 36 individuals with PBC and compensated cirrhosis, since cirrhosis “is an endpoint for virtually all liver diseases,” John Vierling, MD, said in a video interview at the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
To see how this group fared, Dr. Vierling and his coinvestigators performed a post hoc analysis of the POISE data to examine OCA’s safety and efficacy for patients with compensated cirrhosis. Patients with decompensated cirrhosis were not included in the trial.
Dr. Vierling, chief of hepatology at Baylor College of Medicine, Houston, noted that investigators worked hard to set the bar high for inclusion in the group with cirrhosis, to achieve very high specificity. “We did this by using very stringent criteria of liver biopsy, or transient elastography adjusted for a very high range of kilopascals required to diagnose cirrhosis in cholestatic patients,” he said. To be included, patients also had to have elevated total bilirubin levels and a baseline alkaline phosphatase level greater than five times the upper limit of normal.
Statistically, the patients were evenly distributed across the placebo arm and the two treatment arms, one of which dosed OCA at 10 mg/day; the other treatment arm had flexible dosing at 5-10 mg/day.
The POISE trial used a composite primary efficacy endpoint of achieving an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal, with total bilirubin within normal limits, and at least a 15% reduction in ALP.
“Significantly more OCA-treated patients with cirrhosis achieved the primary composite endpoint compared to placebo,” Dr. Vierling and his coauthors wrote in a poster presented at the annual meeting for the American Association for the Study of Liver Diseases. The difference was individually significant for all three values that made up the composite primary endpoint as well.
Secondary endpoints included gamma-glutamyltransferase, alanine aminotrasferase, and aspartate aminotransferase, all of which were significantly reduced among patients taking OCA. Patients on placebo saw these values rise over the time period of the study.
There were no new safety signals seen in the post hoc analysis of the group with cirrhosis that were not seen in the trial at large, said Dr. Vierling. Two individuals in the subgroup dropped out of the trial because of pruritis, a similar proportion to that seen in the full trial population.
The drug’s manufacturer, Intercept Pharmaceuticals, is working with the Food and Drug Administration to establish appropriate doses and intervals for obeticholic acid so it may be used safely in individuals with decompensated cirrhosis, said Dr. Vierling.
Obeticholic acid, a farnesoid-X receptor agonist, is an approved agent to use as add-on therapy to ursodeoxycholic acid (UDCA), or as monotherapy for patients who can’t tolerate UDCA.
Dr. Vierling disclosed financial relationships with Intercept Pharmaceuticals and with several other pharmaceutical companies. The study was funded by Intercept Pharmaceuticals.
[email protected]
On Twitter @karioakes
BOSTON – Patients with primary biliary cholangitis (PBC) who have compensated cirrhosis fared just as well on obeticholic acid (OCA) as did PBC patients without cirrhosis, according to an analysis of data from POISE, the pivotal clinical trial for approval of OCA for PBC.
The POISE trial included 36 individuals with PBC and compensated cirrhosis, since cirrhosis “is an endpoint for virtually all liver diseases,” John Vierling, MD, said in a video interview at the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
To see how this group fared, Dr. Vierling and his coinvestigators performed a post hoc analysis of the POISE data to examine OCA’s safety and efficacy for patients with compensated cirrhosis. Patients with decompensated cirrhosis were not included in the trial.
Dr. Vierling, chief of hepatology at Baylor College of Medicine, Houston, noted that investigators worked hard to set the bar high for inclusion in the group with cirrhosis, to achieve very high specificity. “We did this by using very stringent criteria of liver biopsy, or transient elastography adjusted for a very high range of kilopascals required to diagnose cirrhosis in cholestatic patients,” he said. To be included, patients also had to have elevated total bilirubin levels and a baseline alkaline phosphatase level greater than five times the upper limit of normal.
Statistically, the patients were evenly distributed across the placebo arm and the two treatment arms, one of which dosed OCA at 10 mg/day; the other treatment arm had flexible dosing at 5-10 mg/day.
The POISE trial used a composite primary efficacy endpoint of achieving an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal, with total bilirubin within normal limits, and at least a 15% reduction in ALP.
“Significantly more OCA-treated patients with cirrhosis achieved the primary composite endpoint compared to placebo,” Dr. Vierling and his coauthors wrote in a poster presented at the annual meeting for the American Association for the Study of Liver Diseases. The difference was individually significant for all three values that made up the composite primary endpoint as well.
Secondary endpoints included gamma-glutamyltransferase, alanine aminotrasferase, and aspartate aminotransferase, all of which were significantly reduced among patients taking OCA. Patients on placebo saw these values rise over the time period of the study.
There were no new safety signals seen in the post hoc analysis of the group with cirrhosis that were not seen in the trial at large, said Dr. Vierling. Two individuals in the subgroup dropped out of the trial because of pruritis, a similar proportion to that seen in the full trial population.
The drug’s manufacturer, Intercept Pharmaceuticals, is working with the Food and Drug Administration to establish appropriate doses and intervals for obeticholic acid so it may be used safely in individuals with decompensated cirrhosis, said Dr. Vierling.
Obeticholic acid, a farnesoid-X receptor agonist, is an approved agent to use as add-on therapy to ursodeoxycholic acid (UDCA), or as monotherapy for patients who can’t tolerate UDCA.
Dr. Vierling disclosed financial relationships with Intercept Pharmaceuticals and with several other pharmaceutical companies. The study was funded by Intercept Pharmaceuticals.
[email protected]
On Twitter @karioakes
BOSTON – Patients with primary biliary cholangitis (PBC) who have compensated cirrhosis fared just as well on obeticholic acid (OCA) as did PBC patients without cirrhosis, according to an analysis of data from POISE, the pivotal clinical trial for approval of OCA for PBC.
The POISE trial included 36 individuals with PBC and compensated cirrhosis, since cirrhosis “is an endpoint for virtually all liver diseases,” John Vierling, MD, said in a video interview at the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
To see how this group fared, Dr. Vierling and his coinvestigators performed a post hoc analysis of the POISE data to examine OCA’s safety and efficacy for patients with compensated cirrhosis. Patients with decompensated cirrhosis were not included in the trial.
Dr. Vierling, chief of hepatology at Baylor College of Medicine, Houston, noted that investigators worked hard to set the bar high for inclusion in the group with cirrhosis, to achieve very high specificity. “We did this by using very stringent criteria of liver biopsy, or transient elastography adjusted for a very high range of kilopascals required to diagnose cirrhosis in cholestatic patients,” he said. To be included, patients also had to have elevated total bilirubin levels and a baseline alkaline phosphatase level greater than five times the upper limit of normal.
Statistically, the patients were evenly distributed across the placebo arm and the two treatment arms, one of which dosed OCA at 10 mg/day; the other treatment arm had flexible dosing at 5-10 mg/day.
The POISE trial used a composite primary efficacy endpoint of achieving an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal, with total bilirubin within normal limits, and at least a 15% reduction in ALP.
“Significantly more OCA-treated patients with cirrhosis achieved the primary composite endpoint compared to placebo,” Dr. Vierling and his coauthors wrote in a poster presented at the annual meeting for the American Association for the Study of Liver Diseases. The difference was individually significant for all three values that made up the composite primary endpoint as well.
Secondary endpoints included gamma-glutamyltransferase, alanine aminotrasferase, and aspartate aminotransferase, all of which were significantly reduced among patients taking OCA. Patients on placebo saw these values rise over the time period of the study.
There were no new safety signals seen in the post hoc analysis of the group with cirrhosis that were not seen in the trial at large, said Dr. Vierling. Two individuals in the subgroup dropped out of the trial because of pruritis, a similar proportion to that seen in the full trial population.
The drug’s manufacturer, Intercept Pharmaceuticals, is working with the Food and Drug Administration to establish appropriate doses and intervals for obeticholic acid so it may be used safely in individuals with decompensated cirrhosis, said Dr. Vierling.
Obeticholic acid, a farnesoid-X receptor agonist, is an approved agent to use as add-on therapy to ursodeoxycholic acid (UDCA), or as monotherapy for patients who can’t tolerate UDCA.
Dr. Vierling disclosed financial relationships with Intercept Pharmaceuticals and with several other pharmaceutical companies. The study was funded by Intercept Pharmaceuticals.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM THE LIVER MEETING
VIDEO: Don’t be surprised by weight gain in men after HCV cure
BOSTON – In the new era of direct-acting antiviral (DAA) therapy, physicians will be seeing more and more patients who have achieved a cure of their hepatitis C virus (HCV). Once freed from the burden of a chronic illness, patients feel better and may eat better. Unexpected weight gain and potential associated health effects may be the next set of challenges patients and their physicians will face.
A single-center retrospective study of patients who had achieved sustained virologic response (SVR) after treatment for HCV found a small but significant weight gain in men, but not women. Additionally, according to noninvasive assessments, liver fat increased significantly in men, but not women, after SVR was achieved.
In a study of 63 patients (42 male, 67%) who received DAA treatment for HCV, mean weight gain for men after SVR was 2.8 pounds (range, –26 to +17; P = .0459), and body mass index (BMI) increased by a mean 0.50 kg/m2 (range, –3.6 to +3.33; P = .0176). No significant change was seen for women when pre- and posttreatment measures were compared.
Isaac Wasserman, a medical student at Mount Sinai Medical Center, New York, presented the results of the single-center retrospective study in a poster presentation at the annual meeting of the American Association for the Study of Liver Diseases.
To assess changes in liver fat, Mr. Wasserman and his coinvestigator used results of pre- and posttreatment transient elastography with controlled attenuation parameter (CAP). CAP measures the degree to which the ultrasound signal is attenuated by liver fat, he explained in a video interview.
For men, hepatic steatosis increased by this measure, with CAP measurements up by a mean 18 dB/m (range, –106 to +128, P = .0314). Mr. Wasserman and his colleagues wrote, “The change in liver fat was large enough to push 11% of the cohort (n = 7 of 63) into advanced steatosis (CAP greater than 300 dB/m).” Again, the women studied had no significant posttreatment change in liver fat.
Post-SVR weight gain appeared to be the culprit in the increased fat seen in the posttreatment livers. Mr. Wasserman and his colleagues in the abstract accompanying the presentation, “Changes in weight were positively correlated with changes in liver fat (P = .006).”
Mr. Wasserman said that he and his coinvestigators believe that social, and not biochemical or mechanistic, reasons underlie the weight gain and increased hepatic steatosis. They are planning further investigation of social and economic factors that may underlie the difference seen in this study, and hope to continue and expand data acquisition to validate their findings.
Mr. Wasserman reported no conflicts of interest or outside sources of funding for the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @karioakes
BOSTON – In the new era of direct-acting antiviral (DAA) therapy, physicians will be seeing more and more patients who have achieved a cure of their hepatitis C virus (HCV). Once freed from the burden of a chronic illness, patients feel better and may eat better. Unexpected weight gain and potential associated health effects may be the next set of challenges patients and their physicians will face.
A single-center retrospective study of patients who had achieved sustained virologic response (SVR) after treatment for HCV found a small but significant weight gain in men, but not women. Additionally, according to noninvasive assessments, liver fat increased significantly in men, but not women, after SVR was achieved.
In a study of 63 patients (42 male, 67%) who received DAA treatment for HCV, mean weight gain for men after SVR was 2.8 pounds (range, –26 to +17; P = .0459), and body mass index (BMI) increased by a mean 0.50 kg/m2 (range, –3.6 to +3.33; P = .0176). No significant change was seen for women when pre- and posttreatment measures were compared.
Isaac Wasserman, a medical student at Mount Sinai Medical Center, New York, presented the results of the single-center retrospective study in a poster presentation at the annual meeting of the American Association for the Study of Liver Diseases.
To assess changes in liver fat, Mr. Wasserman and his coinvestigator used results of pre- and posttreatment transient elastography with controlled attenuation parameter (CAP). CAP measures the degree to which the ultrasound signal is attenuated by liver fat, he explained in a video interview.
For men, hepatic steatosis increased by this measure, with CAP measurements up by a mean 18 dB/m (range, –106 to +128, P = .0314). Mr. Wasserman and his colleagues wrote, “The change in liver fat was large enough to push 11% of the cohort (n = 7 of 63) into advanced steatosis (CAP greater than 300 dB/m).” Again, the women studied had no significant posttreatment change in liver fat.
Post-SVR weight gain appeared to be the culprit in the increased fat seen in the posttreatment livers. Mr. Wasserman and his colleagues in the abstract accompanying the presentation, “Changes in weight were positively correlated with changes in liver fat (P = .006).”
Mr. Wasserman said that he and his coinvestigators believe that social, and not biochemical or mechanistic, reasons underlie the weight gain and increased hepatic steatosis. They are planning further investigation of social and economic factors that may underlie the difference seen in this study, and hope to continue and expand data acquisition to validate their findings.
Mr. Wasserman reported no conflicts of interest or outside sources of funding for the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @karioakes
BOSTON – In the new era of direct-acting antiviral (DAA) therapy, physicians will be seeing more and more patients who have achieved a cure of their hepatitis C virus (HCV). Once freed from the burden of a chronic illness, patients feel better and may eat better. Unexpected weight gain and potential associated health effects may be the next set of challenges patients and their physicians will face.
A single-center retrospective study of patients who had achieved sustained virologic response (SVR) after treatment for HCV found a small but significant weight gain in men, but not women. Additionally, according to noninvasive assessments, liver fat increased significantly in men, but not women, after SVR was achieved.
In a study of 63 patients (42 male, 67%) who received DAA treatment for HCV, mean weight gain for men after SVR was 2.8 pounds (range, –26 to +17; P = .0459), and body mass index (BMI) increased by a mean 0.50 kg/m2 (range, –3.6 to +3.33; P = .0176). No significant change was seen for women when pre- and posttreatment measures were compared.
Isaac Wasserman, a medical student at Mount Sinai Medical Center, New York, presented the results of the single-center retrospective study in a poster presentation at the annual meeting of the American Association for the Study of Liver Diseases.
To assess changes in liver fat, Mr. Wasserman and his coinvestigator used results of pre- and posttreatment transient elastography with controlled attenuation parameter (CAP). CAP measures the degree to which the ultrasound signal is attenuated by liver fat, he explained in a video interview.
For men, hepatic steatosis increased by this measure, with CAP measurements up by a mean 18 dB/m (range, –106 to +128, P = .0314). Mr. Wasserman and his colleagues wrote, “The change in liver fat was large enough to push 11% of the cohort (n = 7 of 63) into advanced steatosis (CAP greater than 300 dB/m).” Again, the women studied had no significant posttreatment change in liver fat.
Post-SVR weight gain appeared to be the culprit in the increased fat seen in the posttreatment livers. Mr. Wasserman and his colleagues in the abstract accompanying the presentation, “Changes in weight were positively correlated with changes in liver fat (P = .006).”
Mr. Wasserman said that he and his coinvestigators believe that social, and not biochemical or mechanistic, reasons underlie the weight gain and increased hepatic steatosis. They are planning further investigation of social and economic factors that may underlie the difference seen in this study, and hope to continue and expand data acquisition to validate their findings.
Mr. Wasserman reported no conflicts of interest or outside sources of funding for the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @karioakes
AT THE LIVER MEETING
It’s not easy to identify clinical depression in menopause
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
The notion that women in midlife are moody is so pervasive that entire Pinterest boards and Facebook pages are dedicated to menopause jokes. For physicians, however, it’s not always so easy to sort out when a patient who says she’s down, or short tempered, might really have major depressive disorder or another serious psychiatric diagnosis.
“The key point is that depressive symptoms are not the same as clinical depression,” said Hadine Joffe, MD, in an interview that recapped her recent presentation at the annual meeting of the North American Menopause Society (NAMS). “The causal factors and contributions to depressive symptoms and major depression are different.”
Practically speaking, this means two things. The first message is that treating common menopausal symptoms can have a positive impact on mood. However, it’s also true that clinicians must be educated and vigilant about more serious mood symptoms, and not expect major depression to lift when a patient starts hormone therapy, according to Dr. Joffe, a psychiatrist and director of the women’s hormone and aging research program at Brigham and Women’s Hospital, Boston.
Using a novel experimental model, Dr. Joffe and her coinvestigators recently completed work that examined the relationship among daytime and nighttime hot flashes, sleep disturbance, and mood changes. In a small study of 29 healthy premenopausal women, they tracked mood, hormone levels, and sleep fragmentation both before and after suppressing ovarian function with a gonadotropin-releasing hormone agonist. The study found independent and significant effects on mood for nighttime (but not daytime) hot flashes, as well as subjective sleep disturbance (J Clin Endocrinol Metab. 2016;101[10]:3847-55).
“We were struck by the fact that the nighttime hot flashes, separate from the sleep problems, contributed to mood symptoms,” Dr. Joffe said.
This study, though small, validates and extends the notion that multiple symptoms of the menopausal transition contribute to the mild mood symptoms that are common during this phase of a woman’s life, said Dr. Joffe. To date, most of the studies have been large epidemiologic studies, which while important, tend to assess people at one cross-sectional time point annually, and can’t always capture a nuanced and precise view of symptoms and how they relate to hormone levels, she said.
“Perimenopausal hormone changes are dynamic,” said Dr. Joffe, and have wide interindividual variation during the menopausal transition. Overall, though, she said, “clinical studies show that mood is better as ovarian activity is more normalized in perimenopausal women. Conversely, the more abnormal the hormonal profile, the worse the mood.”
Major depression is another story, said Dr. Joffe. “Menopause-specific factors have not, for the most part, been linked,” she said, noting that the best predictors for clinical depression in midlife that have been identified to date are a previous history of clinical depression or anxiety, as well as other traditional psychiatric risk factors such as low socioeconomic status and a low level of social support.
“People often present with all these symptoms all at once; they have mood disturbances, they have hot flashes, they have sleep disturbances. For the people experiencing these symptoms, it matters a lot to be able to have an explanation that’s credible, and defendable, and evidence based,” Dr. Joffe said. “And it also has implications for treatment, of course.”
This real world complexity inevitably intrudes during a clinical encounter, and it’s not an easy task, or a quick one, to tease apart the extent to which the menopausal transition is contributing to depressive symptoms when women have so many other potential stressors.
While acknowledging that it’s very difficult to unpack this in a brief clinic visit, Dr. Shifren also emphasized that it’s critically important. For patients with mild depressive symptoms, hormone therapy or other treatment to address vasomotor symptoms, along with evidence-based treatment of sleep problems, can be of real help.
“That’s very different from women who come in with real depression,” Dr. Shifren said in an interview. “It’s very important not to say, ‘Oh, that’s just a little bit of perimenopause.’ ”
“There is not enough education of general providers about the nuances of mood changes and mental health of women in midlife,” Dr. Montgomery said in an interview. “These are nicely dealt with in publications of the North American Menopause Society,” he said, also noting that the ob.gyn. residency curriculum at Drexel University includes specific modules to address the menopausal transition and menopause. “If you are going to be caring for women in transition, you probably should do a little deeper dive,” he said.
“My advice for clinicians is don’t do this alone,” Dr. Shifren said. If clinicians feel they lack expertise in diagnosing and managing mood disorders, they should establish collaborative relationships with colleagues in mental health. “We can still help with hormone management, sleep management, and keeping in touch with the patient,” she said.
One trick of the trade is to use your nursing staff to follow up with patients, Dr. Shifren said. She will ask a nurse to make a follow-up phone call 2-6 weeks after a patient visit to assess how the woman is faring with symptoms and any treatments that have been initiated or modified. The interval and intensity of follow-up can be modified based on feedback from this call, she said.
The bottom line for Dr. Montgomery is twofold: “Being menopausal does not make you depressed,” he said. “True clinical depression is a rare event, but one that should not be missed.”
Dr. Joffe reported consulting agreements with several pharmaceutical companies, and grant support from Merck for research related to vasomotor symptoms and insomnia. Dr. Montgomery reported no relevant financial disclosures. Dr. Shifren reported that she has a consulting agreement with the New England Research Institutes.
[email protected]
On Twitter @karioakes
VIDEO: Obeticholic acid resulted in reduction of a biomarker for liver fibrosis in PBC
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
BOSTON – Obeticholic acid resulted in a significant reduction of a biomarker for liver fibrosis in patients with primary biliary cholangitis, according to a retrospective analysis of clinical trial data. In addition, patients taking obeticholic acid had a mean reduction in liver stiffness as measured by transient elastography.
Gideon Hirschfield, MD, PhD, presented the re-analysis of clinical trial data at the annual meeting of the American Association for the Study of Liver Diseases.
POISE was a phase III randomized, double-blind, placebo-controlled study of obeticholic acid for patients with primary biliary cholangitis (PBC). The clinical trial’s primary composite endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of normal, with at least a 15% reduction in alkaline phosphatase and normal serum bilirubin.
The cohort of POISE patients on obeticholic acid met this biochemical surrogate endpoint, resulting in approval of the farnesoid X receptor agonist for treatment of PBC as an add-on to ursodeoxycholic acid (UDCA), or for patients who cannot tolerate UDCA.
However, transient elastography and the aspartate transaminase (AST) to platelet ratio index (APRI) have both been used to assess fibrosis in PBC, and have been found to predict clinical outcomes in PBC. These measures have the advantage of being noninvasive methods to measure the quality of liver tissue.
Dr. Hirschfield, a transplant hepatologist at the institute of immunology and immunotherapy at the University of Birmingham, England, and his coinvestigators reevaluated data from the POISE trial. They determined that APRI dropped significantly over 12 months of obeticholic acid treatment compared to placebo (P less than .01 for each of the two dosing arms of the POISE trial). Patients who switched to 5-10 mg of obeticholic acid daily from placebo during an open-label extension of POISE also had significant reductions in APRI scores (P less than .05); the reduction for placebo-switchers on a fixed 10-mg dose during the open-label study was not significant
Liver stiffness, as measured by transient elastography, was reduced for both arms of the POISE study at 12 months, but increased for those in the placebo arm. “Fewer patients receiving obeticholic acid 10 mg progressed” to a level associated with histological cirrhosis, “and patients receiving obeticholic acid showed an improvement in liver stiffness,” said Dr. Hirschfield.
Pruritis is a feature of PBC, and worsening pruritis can be a side effect of deoxycholic acid. However, the worsening is often transitory, so patients should be encouraged to try to stay the course, said Dr. Hirschfield. Managing patient expectations; sharing improved biomarkers; and considering the addition of a bile acid sequestrant or rifampicin, or reducing the obeticholic acid dose are all strategies to consider when caring for PBC patients, said Dr. Hirschfield.
Clinical trials to assess the safety and efficacy of obeticholic acid for individuals with nonalcoholic fatty liver disease and steatohepatitis are underway.
Dr. Hirschfield discussed his findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @karioakes
AT THE LIVER MEETING 2016
New scale bests Milan criteria in predicting posttransplant HCC recurrence
BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.
The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).
The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.
In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).
Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.
Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.
The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.
This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.
To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.
The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.
The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.
In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.
RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.
Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.
“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.
Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.
The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.
This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.
Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.
The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.
[email protected]
On Twitter @karioakes
BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.
The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).
The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.
In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).
Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.
Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.
The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.
This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.
To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.
The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.
The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.
In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.
RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.
Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.
“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.
Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.
The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.
This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.
Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.
The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.
[email protected]
On Twitter @karioakes
BOSTON – A new scoring system fared better than the Milan criteria in predicting risk for recurrent hepatocellular carcinoma after liver transplant.
The scoring system combines an assessment of the number and size of tumors on the explanted liver with serum alpha-fetoprotein (AFP) score and the presence of microvascular invasion to assign a numeric risk score to patients who have received liver transplant for hepatocellular carcinoma (HCC).
The risk estimation tool showed good model estimation, with a C statistic of 0.82 (95% confidence interval, 0.77-0.86), according to Neil Mehta, MD, who presented the study validating the risk estimation tool at the annual meeting of the American Association for the Study of Liver Diseases. The C statistic is a measure of goodness of fit, with values closer to 1 indicating better fit.
In a paper published simultaneously in JAMA Oncology, Dr. Mehta and his collaborators said that the tool had “superior recurrence risk classification, compared with explant Milan criteria (net reclassification index, 0.40; P = 0.001) in the study’s validation cohort” (JAMA Oncol. 2016 Nov 13. doi: 10:1001/jamaoncol2016/5116).
Under the Milan criteria, patients with HCC are eligible for liver transplant if there are no extrahepatic manifestations and no vascular invasion. One lesion must be smaller than 5 cm, and up to three lesions smaller than 3 cm are permitted.
Dr. Mehta, a gastroenterologist and transplant hepatologist at the University of California, San Francisco, worked with colleagues to narrow down a long list of factors that in previous studies had been associated with HCC recurrence. The final Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score uses just three factors that multivariable analysis found were most highly predictive of HCC recurrence after liver transplant.
The three factors are microvascular invasion; AFP at the time of liver transplant; and the sum of the largest viable tumor diameter plus the number of viable tumors, assessed at the time of explant.
This last factor uses pathology examination, rather than radiology results, to assess tumor number, size, and viability. If a tumor is found to be completely necrotic, for example, it is not included when counting tumors for this component of the RETREAT score.
To develop the scoring system, Dr. Mehta and his coauthors enrolled adult patients with HCC who had liver transplant at three centers, each with a different wait time for transplant – short, medium, or long. Patients in the development cohort (n=721) had Model for End-Stage Liver Disease (MELD) score exception, and patients always met Milan criteria on imaging.
The validation cohort (n=340) had the same inclusion and exclusion criteria, but differed in several significant ways from the development cohort, with more young people, men, and individuals with hepatitis B or alcohol abuse. Individuals in the validation cohort were less likely to have received locoregional therapy (LRT) before liver transplant, but were more likely to have had a single tumor. They had more microvascular invasion, more tumors that were poorly differentiated, and more tumor staging beyond Milan criteria on explant.
The primary outcome measures for the study were overall survival and 5-year post–liver transplant HCC recurrence.
In developing the RETREAT scoring system, investigators used the final multivariable model coefficients to produce a “simplified point scale reflecting the relative impact of model covariables,” Dr. Mehta and his coauthors wrote.
RETREAT scoring ranges from 0 to 8; in the studied patients, the most common score was 1. Any microvascular invasion is assigned a point value of 2. The sum of the largest viable tumor diameter – in centimeters – plus the number of viable tumors is divided into four categories. If there are no tumors, the score is 0. For a sum of 1.1-4.9, the score is 1; a sum of 5.0-9.9 is assigned a score of 2, and a sum or 10 or greater is assigned a score of 3.
Serum AFP at the time of liver transplant (measured in ng/mL) is given a score of 0 if the value is less than 20. AFP of 20-99 is assigned a score of 1, values of 100-999 a score of 2, and 1,000 or greater a score of 3.
“Predicted risk of 1- and 5-year HCC recurrence rose with each point scored such that a patient with a RETREAT score of 5 or higher … had a predicted 1- and 5-year recurrence risk of 39.3 (95% CI, 25.5%-50.5%) and 75.2% (95% CI, 56.7%-85.8%), respectively,” the researchers wrote.
Dr. Mehta and his coauthors emphasized that the RETREAT scoring system represents an effort to strike a balance between including clinically meaningful variables to predict HCC recurrence and retaining simplicity and ease of use.
The researchers suggested guidelines for post–liver transplant HCC recurrence surveillance based on RETREAT scoring. They recommend no follow-up for a score of 0; surveillance scans and AFP monitoring every 6 months for 2 years for a score of 1-3, and every 6 months for 5 years for a score of 4. RETREAT scores of 5 or higher warrant surveillance every 3-4 months for 2 years, followed by every 6 months through year 5.
This surveillance stratification, they said, should help control costs while retaining a vigilant approach for those most at risk of recurrence. This approach is currently in use at University of California, San Francisco.
Study limitations included some missing information on AFP levels in the development cohort, and a small number of missing histologic tumor grading in both cohorts. In order to address limitations in the retrospective design of the present study, Dr. Mehta and his coauthors are planning another multicenter study to evaluate RETREAT as a surveillance tool and confirm its prognostic value.
The authors reported no conflicts of interest. The study was funded by the Biostatistics Core of the UCSF Liver Center.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: The RETREAT score was superior to explant Milan criteria in predicting post–liver transplant HCC recurence (P = .001)
Data source: Multivariable analysis of prognostic factors for HCC recurrence in a group of 721 patients in a development cohort and 340 in a validation cohort, all of whom had liver transplant.
Disclosures: The study investigators reported no disclosures. The study was funded by the Biostatistics Core of the University of California, San Francisco Liver Center.