User login
Recurrent acute pancreatitis significantly impairs both mental and physical quality of life
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
CHICAGO – Despite its intermittent and unpredictable nature, recurrent acute pancreatitis exacts a significant toll on patients’ physical and mental quality of life.
It is well-known that patients with chronic pancreatitis suffer physically and emotionally. However, the same understanding has not been engendered for those who experience recurrent acute pancreatitis (RAP), Gregory A. Cote, MD, said at the annual Digestive Disease Week®. Sporadic episodes of acute pancreatitis may cause persistent declines in quality of life.
“RAP clearly leads to a significant reduction in physical and mental quality of life, despite its erratic and sporadic nature,” Dr. Cote said. “Smoking and self-reported disability are very important drivers of these reductions, and a concomitant diagnosis of diabetes exacerbates that even further.”
To explore RAP’s impact on mental and physical quality of life, Dr. Cote examined data from three related cross-sectional North American Pancreatitis Studies (NAPS): the NAPS2, NAPS2-CV (Continuation and Validation), and NAPS2-AS (Ancillary Study).
These studies comprised 2,619 subjects who were enrolled at 27 U.S. sites from 2000 to 2014. Both patients and their physicians completed detailed baseline questionnaires that included personal and family history, risk factors, symptoms, and the 12-Item Short Form Health Survey (SF-12), a detailed quality of life measure.
A score of 50 is the mean for the U.S. general population, and a difference of 3 points or more is considered clinically relevant, Dr. Cote noted.
He parsed the cohort into three groups: those with RAP (508), those with chronic pancreatitis (1,086), and a reference group of healthy controls who were also in the database (1,025).
Some significant between-group differences were immediately obvious, Dr. Cote said. Patients with RAP were significantly younger than both chronic pancreatitis patients (CP) and controls (45 vs. 51 and 49 years, respectively). They also experienced their first bout of acute pancreatitis sooner than CP patients became symptomatic (40 vs. 44 years). Gender was a factor as well: CP patients were more often men (55% vs. 46%).
The pattern of alcohol use between the groups was difficult to interpret, he said. About one-quarter of RAP patients abstained, another fourth were light drinkers, and another fourth moderate drinkers – 12% drank heavily and 7% very heavily. In contrast, frequent drinking was more common among CP patients, with 12% reporting that they drank heavily and 33% very heavily.
CP patients were significantly more likely to be smokers, with 75% reporting current or past tobacco use, compared with 55% of RAP patients. More RAP patients reported never smoking (44% vs. 25%).
RAP patients fell between CP patients and controls in terms of medical comorbidities, including diabetes, renal disease or kidney failure, heart disease, and liver disease.
On the SF-12 physical component section, RAP patients scored a mean of 41 points – significantly worse than controls (51) but significantly better than CP patients (37). The findings were similar for the mental component score: RAP patients scored a mean of 45, compared with 52 in controls and 43 in CP patients.
Dr. Cote performed a multivariate analysis that controlled for age, sex, tobacco and alcohol use, and diabetes. Again, he found that, compared with controls, RAP was associated with significantly reduced scores on both the physical and mental components (mean 8.5 and 6.5 points, respectively).
“The magnitude of reduction was even greater for chronic pancreatitis, with an 11-point reduction on the physical component score and a 7.6-point reduction on the mental component score.
He then sought to identify which clinical characteristics most contributed to this impact on quality of life.
On the physical component score, several were significant, including female sex, which was associated with a 4.4-point decrease; prior pancreatic surgery (–3.3); endocrine insufficiency (–4.6); past smoking (–2.5); current smoking (–3.6); and self-reported physical disability (–9.5).
The mental component score breakdown echoed some of these. Self-reported disability exerted the largest impact, bringing the mental score down by a mean of 5.4 points. Other significant factors were smoking less than a pack a day (–2.5) and smoking more than a pack a day (–4.6). Any suspicion of chronic pancreatitis by the treating physician was associated with a 2.9-point decrease on the score.
“Our findings stress that this is not a disease that can be followed conservatively. We have to investigate interventions that will attenuate it, not only because these patients may go on to develop chronic pancreatitis but because, in their current state, most are experiencing significant reductions in their quality of life.”
Dr Cote had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: On a physical QOL scale, patients scored a mean of 41 points – 10 points lower than controls. The mental QOL score was 7 points lower.
Data source: The database review comprised 2,619 subjects.
Disclosures: Dr. Cote had no financial disclosures.
Half of newly detected antimicrobial antibodies do not lead to PBC
Nearly half of newly detected antimitochondrial antibodies (AMAs) in clinical practice do not lead to a diagnosis of primary biliary cholangitis (PBC), according to a prospective study.
Geraldine Dahlqvist, MD, and her associates examined 720 patients whose AMA tests were registered during a 1-year census period. They were divided into groups according to whether they were newly diagnosed (275), were previously diagnosed (216), or had a nonestablished diagnosis (229) of PBC. Results showed the prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000 inhabitants. It was four (all AMA-positive patients) to six (PBC patients) times higher in women than in men. The median age was 58 years, with the median AMA titer at 1:16. Normal serum alkaline phosphatases (ALP) were 74%, and were 1.5 times above the upper limit of normal in 13% of patients, while cirrhosis was found in 6%. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%.
It was noted that no patients died officially from PBC in this study. The 1-, 3-, and 5-year rates of survival were 95%, 90%, and 75% (95% CI, 63-87), respectively, compared with 90% in the control group.
“The younger age and lower autoantibody titer of these patients, together with the frequent mild abnormalities of their biochemical liver tests, supports a very early, presymptomatic precholestatic stage of the disease,” Dr. Dahlqvist, of Catholic University of Louvain (Belgium), and her colleagues noted. “The incidence of clinical manifestations of PBC seems, however, much lower than previously reported.”
Find the full story in Hepatology (doi: 10.1002/hep.28559).
Nearly half of newly detected antimitochondrial antibodies (AMAs) in clinical practice do not lead to a diagnosis of primary biliary cholangitis (PBC), according to a prospective study.
Geraldine Dahlqvist, MD, and her associates examined 720 patients whose AMA tests were registered during a 1-year census period. They were divided into groups according to whether they were newly diagnosed (275), were previously diagnosed (216), or had a nonestablished diagnosis (229) of PBC. Results showed the prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000 inhabitants. It was four (all AMA-positive patients) to six (PBC patients) times higher in women than in men. The median age was 58 years, with the median AMA titer at 1:16. Normal serum alkaline phosphatases (ALP) were 74%, and were 1.5 times above the upper limit of normal in 13% of patients, while cirrhosis was found in 6%. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%.
It was noted that no patients died officially from PBC in this study. The 1-, 3-, and 5-year rates of survival were 95%, 90%, and 75% (95% CI, 63-87), respectively, compared with 90% in the control group.
“The younger age and lower autoantibody titer of these patients, together with the frequent mild abnormalities of their biochemical liver tests, supports a very early, presymptomatic precholestatic stage of the disease,” Dr. Dahlqvist, of Catholic University of Louvain (Belgium), and her colleagues noted. “The incidence of clinical manifestations of PBC seems, however, much lower than previously reported.”
Find the full story in Hepatology (doi: 10.1002/hep.28559).
Nearly half of newly detected antimitochondrial antibodies (AMAs) in clinical practice do not lead to a diagnosis of primary biliary cholangitis (PBC), according to a prospective study.
Geraldine Dahlqvist, MD, and her associates examined 720 patients whose AMA tests were registered during a 1-year census period. They were divided into groups according to whether they were newly diagnosed (275), were previously diagnosed (216), or had a nonestablished diagnosis (229) of PBC. Results showed the prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000 inhabitants. It was four (all AMA-positive patients) to six (PBC patients) times higher in women than in men. The median age was 58 years, with the median AMA titer at 1:16. Normal serum alkaline phosphatases (ALP) were 74%, and were 1.5 times above the upper limit of normal in 13% of patients, while cirrhosis was found in 6%. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%.
It was noted that no patients died officially from PBC in this study. The 1-, 3-, and 5-year rates of survival were 95%, 90%, and 75% (95% CI, 63-87), respectively, compared with 90% in the control group.
“The younger age and lower autoantibody titer of these patients, together with the frequent mild abnormalities of their biochemical liver tests, supports a very early, presymptomatic precholestatic stage of the disease,” Dr. Dahlqvist, of Catholic University of Louvain (Belgium), and her colleagues noted. “The incidence of clinical manifestations of PBC seems, however, much lower than previously reported.”
Find the full story in Hepatology (doi: 10.1002/hep.28559).
FROM HEPATOLOGY
Mild, moderate hypertriglyceridemia raises pancreatitis risk
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.
Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.
To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.
The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).
This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.
This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Mild to moderate hypertriglyceridemia is associated with increased risk of acute pancreatitis.
Major finding: Compared with normal triglyceride levels of less than 89 mg/dL, the risk for acute pancreatitis increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above.
Data source: A prospective, longitudinal cohort study involving 116,550 adults followed for 6.7 years.
Disclosures: This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.
Thyroid disease does not affect primary biliary cholangitis complications
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.
“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).
Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.
“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”
No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.
Key clinical point:
Major finding: 150 of 921 PBC patients had TD (16.3%), but there was no correlation between PBC patients who had TD and their histologic stage either at diagnosis, hepatic decompensation events, occurrence of hepatocelluler carcinoma, or liver transplantation rates.
Data source: Prospective study of 921 PBC patients in Padua and Barcelona from 1975 to 2015.
Disclosures: No funding source was disclosed; authors reported no relevant financial disclosures.
PBC patients show brain abnormalities before cirrhosis occurs
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.
In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.
An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.
“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.
Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Causes of recurrent pediatric pancreatitis start to emerge
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Overall, 17 of 83 patients (20%) had recurrent acute pancreatitis, but among six patients with a genetic cause, five had recurrences.
Data source: Eighty-three patients enrolled in INSPPIRE, an international consortium formed to prospectively study pediatric pancreatitis.
Disclosures: Dr. Sweeny had no disclosures.
Biomarker identifies precancerous pancreatic cysts
LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.
If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.
Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.
The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.
The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.
By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.
A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.
“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.
Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.
If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.
Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.
The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.
The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.
By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.
A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.
“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.
Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.
If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.
Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.
The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.
The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.
By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.
A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.
“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.
Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
AT ACG 2016
Key clinical point:
Major finding: DNA markers isolated from pancreatic fluid predicted cancer or high-grade dysplasia with 90% specificity and 93% sensitivity.
Data source: Pilot study, retrospective analysis.
Disclosures: Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
Young patients suffer most from PBC
Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.
The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.
There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.
Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).
The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.
QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.
Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.
“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.
QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.
The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.
Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.
Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.
This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.
Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.
The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.
There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.
Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).
The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.
QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.
Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.
“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.
QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.
The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.
Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.
Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.
This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.
Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.
The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.
There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.
Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).
The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.
QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.
Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.
“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.
QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.
The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.
Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.
Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.
This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.
FROM ALIMENTARY PHARMACOLOGY AND THERAPEUTICS
Key clinical point:
Major finding: There was a linear relationship between age and quality of life (QoL) in patients with primary biliary cholangitis, with younger presenting patients having the poorest QoL. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL.
Data source: Review of 1,990 patients in the United Kingdom–PBC cohort.
Disclosures: The work was funded by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, and Novartis.
Pancreaticobiliary potpourri
The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”
Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.
I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.
This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.
The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”
Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.
I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.
This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.
The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”
Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.
I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.
This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.
Two incretin-based drugs linked to increased bile duct disease but not pancreatitis
At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.
Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.
Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.
The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.
Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).
The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.
Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.
“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”
Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.
When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.
The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.
However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).
Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.
“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.
DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.
“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”
The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.
The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.
At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.
Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.
Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.
The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.
Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).
The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.
Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.
“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”
Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.
When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.
The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.
However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).
Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.
“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.
DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.
“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”
The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.
The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.
At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.
Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.
Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.
The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.
Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).
The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.
Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.
“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”
Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.
When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.
The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.
However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).
Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.
“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.
DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.
“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”
The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.
The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Glucagon-like peptide 1 agonists do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.
Major finding: GLP-1 agonists are associated with a 79% increase in the risk of bile duct and gallbladder disease, compared with other oral antidiabetic medications, but do not increase the risk of acute pancreatitis.
Data source: Two population-based cohort studies; one involving more than 1.5 million individuals with type 2 diabetes across three countries, and the other involving 71,368 patients with type 2 diabetes.
Disclosures: The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared. The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.