User login
High mortality seen in acute-on-chronic liver failure
An attempt to define and classify acute-on-chronic liver failure showed that the syndrome carries a 28-day mortality rate that is 15 times greater than in cirrhosis patients who do not have the syndrome.
Moreover, the syndrome is extremely common, and may be found in nearly one-third of acutely decompensated cirrhosis patients, wrote Dr. Richard Moreau and colleagues. The study was published in the June issue of Gastroenterology.
Source: American Gastroenterological Association
"A universally accepted and used definition of acute-on-chronic liver failure (ACLF) is still lacking," said Dr. Moreau of Université Paris Diderot, Paris.
"Defining ACLF is not only a matter of nosology, but also is of great importance because it would allow early identification of patients at high risk for end-organ failure–related death, requiring specific treatments and/or intensive management," he added.
To that end, Dr. Moreau looked at 1,343 adult patients hospitalized for at least 1 day who had an acute decompensation of cirrhosis as defined by the acute development of large ascites, hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infection, or any combination of the above.
Patients who were admitted for a scheduled procedure or treatment were excluded from the analysis, as were patients with severe chronic extrahepatic disease and patients with HIV infection.
The study subjects were then divided into four groups. The first group, which was judged not to have ACLF, had no organ failure, a serum creatinine less than 1.5 mg/dL, and no hepatic encephalopathy. This group made up 1,040 of the 1,343 enrolled patients (77.4%), and had 28-day and 90-day mortality rates of 4.7% and 14%, respectively.
The next cohort, called ACLF grade 1, comprised patients with a single coagulation, circulatory or respiratory failure; a serum creatinine between 1.5 and 1.9 mg/dL; and/or mild to moderate hepatic encephalopathy. The 148 patients in this class (11.0%) had 28- and 90-day mortality rates of 22.1% and 40.7%, respectively.
ACLF grade 2 was more severe, with two organ failures; 108 patients (8%) had this at enrollment, and exhibited 28- and 90-day mortality rates of 32.0% and 40.7%, respectively.
The most severely ill patients were classed as having ACLF grade 3, with three organ failures or more. A total of 47 patients (3.5%) fell into this category, and they had 28- and 90-day mortality rates of 76.7% and 79.1%, respectively.
Overall, according to the investigators, patients with ACLF were younger (mean age 56 years versus 58 years in patients without ACLF; P = .02), had a lower mean arterial blood pressure on admittance to the hospital (79 mm Hg versus 85 mm Hg in non-ACLF patients; P less than .001) and more frequently were actively alcoholic.
They also found that patients with ACLF had a significantly higher white cell count (9.7 x 109 compared with 6.6 x 109/L; P less than .001) and plasma C-reactive protein level (40.3 versus 24.9 mg/L; P less than .001) than the group without ACLF.
And finally, in what they called an "outstanding observation," the authors determined that up to 43.6% of patients with ACLF had no precipitating event leading to their acute decompensation, including gastrointestinal hemorrhage, bacterial infection, or active alcoholism.
The authors concluded that their novel diagnostic criteria show that ACLF is "distinct from ‘mere’ AD."
They conceded that their study was not designed to assess ideal management for these patients. "Whether patients with ACLF should be admitted or not to the intensive care unit is controversial," they wrote. "Nevertheless, our results can serve as a resource for designing studies aimed to investigate the appropriate site of hospitalization for patients with ACLF."
The authors disclosed that pharmaceutical companies provided funding for a chronic liver failure consortium, which provided the initiative for this study; several other investigators also disclosed ties with pharmaceutical companies.
The study by Moreau and colleagues represents a culmination of efforts to bring together a continent’s worth of experience in research and patient care into defining an important issue that has been struggling to find a definition: acute-on-chronic liver failure or ACLF. This important study crucially separates ACLF as an entity distinct
from mere decompensation of cirrhosis, something that has long confused the
picture among clinicians. The definition of organ failure, the basis for ACLF,
was determined a priori by expert opinion. The team found a significantly poorer
prognosis in patients with more than two organ failures, especially renal
failure. An intriguing finding was the better prognosis of previously
decompensated cirrhotic patients compared with those without prior
decompensation, which should form the basis for future investigation into the
relationship of ACLF with potential immune tolerance. Other interesting points
raised, such as the absence of precipitating factors in almost half of the ACLF
cases, and correlation of outcomes with leukocyte count and C-reaction protein,
need further corroboration since a large proportion of patients had an
alcoholic etiology. In a large study, it is not always possible to have uniform
precipitating factor investigations. Importantly, these results have also been
corroborated by the initial reports on ACLF using simpler criteria for organ
failure in the North American Consortium for End-Stage Liver Disease (NACSELD).
As the cirrhotic population in Western countries ages along with a scarcity of
donor organs and the emergence of resistant pathogens, the knowledge of ACLF is
going to be increasingly relevant and further large, collaborative studies are
needed along the lines of this paper to tackle this growing issue.
Dr. Jasmohan Bajaj is in the division of gastroenterology, hepatology,
and nutrition at Virginia Commonwealth University and at McGuire VA Medical
Center, Richmond.
His institution has received grants from, and he has been a consultant to,
Grifols, Salix, and Otsuka. He has received an honorarium from Merz.
The study by Moreau and colleagues represents a culmination of efforts to bring together a continent’s worth of experience in research and patient care into defining an important issue that has been struggling to find a definition: acute-on-chronic liver failure or ACLF. This important study crucially separates ACLF as an entity distinct
from mere decompensation of cirrhosis, something that has long confused the
picture among clinicians. The definition of organ failure, the basis for ACLF,
was determined a priori by expert opinion. The team found a significantly poorer
prognosis in patients with more than two organ failures, especially renal
failure. An intriguing finding was the better prognosis of previously
decompensated cirrhotic patients compared with those without prior
decompensation, which should form the basis for future investigation into the
relationship of ACLF with potential immune tolerance. Other interesting points
raised, such as the absence of precipitating factors in almost half of the ACLF
cases, and correlation of outcomes with leukocyte count and C-reaction protein,
need further corroboration since a large proportion of patients had an
alcoholic etiology. In a large study, it is not always possible to have uniform
precipitating factor investigations. Importantly, these results have also been
corroborated by the initial reports on ACLF using simpler criteria for organ
failure in the North American Consortium for End-Stage Liver Disease (NACSELD).
As the cirrhotic population in Western countries ages along with a scarcity of
donor organs and the emergence of resistant pathogens, the knowledge of ACLF is
going to be increasingly relevant and further large, collaborative studies are
needed along the lines of this paper to tackle this growing issue.
Dr. Jasmohan Bajaj is in the division of gastroenterology, hepatology,
and nutrition at Virginia Commonwealth University and at McGuire VA Medical
Center, Richmond.
His institution has received grants from, and he has been a consultant to,
Grifols, Salix, and Otsuka. He has received an honorarium from Merz.
The study by Moreau and colleagues represents a culmination of efforts to bring together a continent’s worth of experience in research and patient care into defining an important issue that has been struggling to find a definition: acute-on-chronic liver failure or ACLF. This important study crucially separates ACLF as an entity distinct
from mere decompensation of cirrhosis, something that has long confused the
picture among clinicians. The definition of organ failure, the basis for ACLF,
was determined a priori by expert opinion. The team found a significantly poorer
prognosis in patients with more than two organ failures, especially renal
failure. An intriguing finding was the better prognosis of previously
decompensated cirrhotic patients compared with those without prior
decompensation, which should form the basis for future investigation into the
relationship of ACLF with potential immune tolerance. Other interesting points
raised, such as the absence of precipitating factors in almost half of the ACLF
cases, and correlation of outcomes with leukocyte count and C-reaction protein,
need further corroboration since a large proportion of patients had an
alcoholic etiology. In a large study, it is not always possible to have uniform
precipitating factor investigations. Importantly, these results have also been
corroborated by the initial reports on ACLF using simpler criteria for organ
failure in the North American Consortium for End-Stage Liver Disease (NACSELD).
As the cirrhotic population in Western countries ages along with a scarcity of
donor organs and the emergence of resistant pathogens, the knowledge of ACLF is
going to be increasingly relevant and further large, collaborative studies are
needed along the lines of this paper to tackle this growing issue.
Dr. Jasmohan Bajaj is in the division of gastroenterology, hepatology,
and nutrition at Virginia Commonwealth University and at McGuire VA Medical
Center, Richmond.
His institution has received grants from, and he has been a consultant to,
Grifols, Salix, and Otsuka. He has received an honorarium from Merz.
An attempt to define and classify acute-on-chronic liver failure showed that the syndrome carries a 28-day mortality rate that is 15 times greater than in cirrhosis patients who do not have the syndrome.
Moreover, the syndrome is extremely common, and may be found in nearly one-third of acutely decompensated cirrhosis patients, wrote Dr. Richard Moreau and colleagues. The study was published in the June issue of Gastroenterology.
Source: American Gastroenterological Association
"A universally accepted and used definition of acute-on-chronic liver failure (ACLF) is still lacking," said Dr. Moreau of Université Paris Diderot, Paris.
"Defining ACLF is not only a matter of nosology, but also is of great importance because it would allow early identification of patients at high risk for end-organ failure–related death, requiring specific treatments and/or intensive management," he added.
To that end, Dr. Moreau looked at 1,343 adult patients hospitalized for at least 1 day who had an acute decompensation of cirrhosis as defined by the acute development of large ascites, hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infection, or any combination of the above.
Patients who were admitted for a scheduled procedure or treatment were excluded from the analysis, as were patients with severe chronic extrahepatic disease and patients with HIV infection.
The study subjects were then divided into four groups. The first group, which was judged not to have ACLF, had no organ failure, a serum creatinine less than 1.5 mg/dL, and no hepatic encephalopathy. This group made up 1,040 of the 1,343 enrolled patients (77.4%), and had 28-day and 90-day mortality rates of 4.7% and 14%, respectively.
The next cohort, called ACLF grade 1, comprised patients with a single coagulation, circulatory or respiratory failure; a serum creatinine between 1.5 and 1.9 mg/dL; and/or mild to moderate hepatic encephalopathy. The 148 patients in this class (11.0%) had 28- and 90-day mortality rates of 22.1% and 40.7%, respectively.
ACLF grade 2 was more severe, with two organ failures; 108 patients (8%) had this at enrollment, and exhibited 28- and 90-day mortality rates of 32.0% and 40.7%, respectively.
The most severely ill patients were classed as having ACLF grade 3, with three organ failures or more. A total of 47 patients (3.5%) fell into this category, and they had 28- and 90-day mortality rates of 76.7% and 79.1%, respectively.
Overall, according to the investigators, patients with ACLF were younger (mean age 56 years versus 58 years in patients without ACLF; P = .02), had a lower mean arterial blood pressure on admittance to the hospital (79 mm Hg versus 85 mm Hg in non-ACLF patients; P less than .001) and more frequently were actively alcoholic.
They also found that patients with ACLF had a significantly higher white cell count (9.7 x 109 compared with 6.6 x 109/L; P less than .001) and plasma C-reactive protein level (40.3 versus 24.9 mg/L; P less than .001) than the group without ACLF.
And finally, in what they called an "outstanding observation," the authors determined that up to 43.6% of patients with ACLF had no precipitating event leading to their acute decompensation, including gastrointestinal hemorrhage, bacterial infection, or active alcoholism.
The authors concluded that their novel diagnostic criteria show that ACLF is "distinct from ‘mere’ AD."
They conceded that their study was not designed to assess ideal management for these patients. "Whether patients with ACLF should be admitted or not to the intensive care unit is controversial," they wrote. "Nevertheless, our results can serve as a resource for designing studies aimed to investigate the appropriate site of hospitalization for patients with ACLF."
The authors disclosed that pharmaceutical companies provided funding for a chronic liver failure consortium, which provided the initiative for this study; several other investigators also disclosed ties with pharmaceutical companies.
An attempt to define and classify acute-on-chronic liver failure showed that the syndrome carries a 28-day mortality rate that is 15 times greater than in cirrhosis patients who do not have the syndrome.
Moreover, the syndrome is extremely common, and may be found in nearly one-third of acutely decompensated cirrhosis patients, wrote Dr. Richard Moreau and colleagues. The study was published in the June issue of Gastroenterology.
Source: American Gastroenterological Association
"A universally accepted and used definition of acute-on-chronic liver failure (ACLF) is still lacking," said Dr. Moreau of Université Paris Diderot, Paris.
"Defining ACLF is not only a matter of nosology, but also is of great importance because it would allow early identification of patients at high risk for end-organ failure–related death, requiring specific treatments and/or intensive management," he added.
To that end, Dr. Moreau looked at 1,343 adult patients hospitalized for at least 1 day who had an acute decompensation of cirrhosis as defined by the acute development of large ascites, hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infection, or any combination of the above.
Patients who were admitted for a scheduled procedure or treatment were excluded from the analysis, as were patients with severe chronic extrahepatic disease and patients with HIV infection.
The study subjects were then divided into four groups. The first group, which was judged not to have ACLF, had no organ failure, a serum creatinine less than 1.5 mg/dL, and no hepatic encephalopathy. This group made up 1,040 of the 1,343 enrolled patients (77.4%), and had 28-day and 90-day mortality rates of 4.7% and 14%, respectively.
The next cohort, called ACLF grade 1, comprised patients with a single coagulation, circulatory or respiratory failure; a serum creatinine between 1.5 and 1.9 mg/dL; and/or mild to moderate hepatic encephalopathy. The 148 patients in this class (11.0%) had 28- and 90-day mortality rates of 22.1% and 40.7%, respectively.
ACLF grade 2 was more severe, with two organ failures; 108 patients (8%) had this at enrollment, and exhibited 28- and 90-day mortality rates of 32.0% and 40.7%, respectively.
The most severely ill patients were classed as having ACLF grade 3, with three organ failures or more. A total of 47 patients (3.5%) fell into this category, and they had 28- and 90-day mortality rates of 76.7% and 79.1%, respectively.
Overall, according to the investigators, patients with ACLF were younger (mean age 56 years versus 58 years in patients without ACLF; P = .02), had a lower mean arterial blood pressure on admittance to the hospital (79 mm Hg versus 85 mm Hg in non-ACLF patients; P less than .001) and more frequently were actively alcoholic.
They also found that patients with ACLF had a significantly higher white cell count (9.7 x 109 compared with 6.6 x 109/L; P less than .001) and plasma C-reactive protein level (40.3 versus 24.9 mg/L; P less than .001) than the group without ACLF.
And finally, in what they called an "outstanding observation," the authors determined that up to 43.6% of patients with ACLF had no precipitating event leading to their acute decompensation, including gastrointestinal hemorrhage, bacterial infection, or active alcoholism.
The authors concluded that their novel diagnostic criteria show that ACLF is "distinct from ‘mere’ AD."
They conceded that their study was not designed to assess ideal management for these patients. "Whether patients with ACLF should be admitted or not to the intensive care unit is controversial," they wrote. "Nevertheless, our results can serve as a resource for designing studies aimed to investigate the appropriate site of hospitalization for patients with ACLF."
The authors disclosed that pharmaceutical companies provided funding for a chronic liver failure consortium, which provided the initiative for this study; several other investigators also disclosed ties with pharmaceutical companies.
FROM GASTROENTEROLOGY
Major finding: Acute-on-chronic liver failure syndrome can be divided into three classes and is distinct from acute decompensation of chronic liver failure.
Data source: Data from 1,343 hospitalized patients with cirrhosis and acute decompensation from February to September 2011 at 29 liver units in eight European countries.
Disclosures: The authors disclosed that pharmaceutical companies provided funding for a chronic liver failure consortium, which provided the initiative for this study; several other investigators also disclosed ties with pharmaceutical companies.
Augmentin implicated in drug-induced liver injury
The crude incidence of drug-induced liver injury is roughly 19.1 cases per 100,000 inhabitants, with amoxicillin-clavulanate the most commonly implicated agent.
That’s according to the second published population-based cohort study of drug-induced liver injury (DILI), wrote Dr. Einar S. Björnsson. The study was published in the June issue of Gastroenterology.
Dr. Björnsson, of the University of Iceland, and colleagues looked at all patients aged older than 15 years hospitalized for liver disease with suspected DILI, plus outpatients at the National University Hospital of Iceland, and all those seen in private practice between March 1, 2010, and Feb. 29, 2012.
Source: American Gastroenterological Association
According to the authors, "In Iceland, every citizen is issued a specific personal identification number that is, among other things, connected to a nationwide pharmaceutical database on outpatient prescriptions."
Therefore, "The study examined the Icelandic Medicines Registry records of prescriptions for all drugs associated with DILI that had at least a possible causal relationship" according to the Roussel Uclaf Causality Assessment Method.
DILI was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal, and/or alkaline phosphatase (ALP) levels greater than two times the upper limit of normal.
Acetaminophen toxicity cases were excluded, though patients with preexisting chronic liver injury were not, if they were considered to have developed superimposed DILI on top of their baseline liver enzyme values.
The authors found that over the study period there were 96 cases eligible for inclusion, including 49 cases in the first year and 47 in the second. That translated into a crude annual incidence during the study period of 19.1 cases per 100,000 inhabitants.
Roughly half were female (56%), and the median age was 55 years (range, 16-91 years).
Looking at the clinical characteristics of the cohort, the authors calculated that only 27% of patients developed jaundice, while 10% of patients complained of rash and 6% of fever. Four of the patients had preexisting liver disease.
Overall, liver injury was judged to be due to a single prescription medication in 75% of cases, most commonly amoxicillin-clavulanate (22%), followed by diclofenac (6%), azathioprine (4%) infliximab (4%), and nitrofurantoin (4%).
By tying the injury to Iceland’s prescription drug database, that meant an incidence of DILI among outpatients of 1 per 133 filled azathioprine prescriptions and 1 in 2,350 amoxicillin-clavulanate users; among inpatients, the incidence of injury attributed to amoxicillin-clavulanate was 1 per 729 patients.
By drug classes, after antibiotics, immunosuppressants were found to be commonly associated with DILI (10%), followed by psychotropic drugs, which accounted for 7% of cases, and then nonsteroidal anti-inflammatory drugs, at 6%, "with diclofenac as the only agent."
Single-drug antineoplastic agents were the causes of DILI in 5% of the cohort, and lipid-lowering agents were the cause in just 3.1% of patients (atorvastatin, n = 2; simvastatin, n = 1).
After injuries due to a single agent, dietary supplements were assumed to be the culprit in 16% of cases, and the use of multiple agents was implicated in 9% of cases.
Looking at outcomes, the researchers reported that DILI was mild in 35 patients (36%), moderate in 55 patients (58%), and severe in 5 patients (5%); there was 1 death, in an 82-year-old patient.
Finally, the median duration from diagnosis of DILI to the normalization of liver enzymes was 64 days, and 7% still had abnormal liver tests 6 months after DILI diagnosis.
According to the authors, the only previously published population-based study, done in France, found an annual crude incidence rate of 13.9 cases per 100,000 inhabitants per year (Hepatology 2002;36:451-5).
They conceded that their rate is somewhat higher; however, "the French study provided no information about the patients at risk for DILI because information about drug consumption was not available," they wrote.
The authors stated that the study was funded by a grant from the National University Hospital of Iceland Research Fund; they disclosed no individual financial conflicts of interest.
The crude incidence of drug-induced liver injury is roughly 19.1 cases per 100,000 inhabitants, with amoxicillin-clavulanate the most commonly implicated agent.
That’s according to the second published population-based cohort study of drug-induced liver injury (DILI), wrote Dr. Einar S. Björnsson. The study was published in the June issue of Gastroenterology.
Dr. Björnsson, of the University of Iceland, and colleagues looked at all patients aged older than 15 years hospitalized for liver disease with suspected DILI, plus outpatients at the National University Hospital of Iceland, and all those seen in private practice between March 1, 2010, and Feb. 29, 2012.
Source: American Gastroenterological Association
According to the authors, "In Iceland, every citizen is issued a specific personal identification number that is, among other things, connected to a nationwide pharmaceutical database on outpatient prescriptions."
Therefore, "The study examined the Icelandic Medicines Registry records of prescriptions for all drugs associated with DILI that had at least a possible causal relationship" according to the Roussel Uclaf Causality Assessment Method.
DILI was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal, and/or alkaline phosphatase (ALP) levels greater than two times the upper limit of normal.
Acetaminophen toxicity cases were excluded, though patients with preexisting chronic liver injury were not, if they were considered to have developed superimposed DILI on top of their baseline liver enzyme values.
The authors found that over the study period there were 96 cases eligible for inclusion, including 49 cases in the first year and 47 in the second. That translated into a crude annual incidence during the study period of 19.1 cases per 100,000 inhabitants.
Roughly half were female (56%), and the median age was 55 years (range, 16-91 years).
Looking at the clinical characteristics of the cohort, the authors calculated that only 27% of patients developed jaundice, while 10% of patients complained of rash and 6% of fever. Four of the patients had preexisting liver disease.
Overall, liver injury was judged to be due to a single prescription medication in 75% of cases, most commonly amoxicillin-clavulanate (22%), followed by diclofenac (6%), azathioprine (4%) infliximab (4%), and nitrofurantoin (4%).
By tying the injury to Iceland’s prescription drug database, that meant an incidence of DILI among outpatients of 1 per 133 filled azathioprine prescriptions and 1 in 2,350 amoxicillin-clavulanate users; among inpatients, the incidence of injury attributed to amoxicillin-clavulanate was 1 per 729 patients.
By drug classes, after antibiotics, immunosuppressants were found to be commonly associated with DILI (10%), followed by psychotropic drugs, which accounted for 7% of cases, and then nonsteroidal anti-inflammatory drugs, at 6%, "with diclofenac as the only agent."
Single-drug antineoplastic agents were the causes of DILI in 5% of the cohort, and lipid-lowering agents were the cause in just 3.1% of patients (atorvastatin, n = 2; simvastatin, n = 1).
After injuries due to a single agent, dietary supplements were assumed to be the culprit in 16% of cases, and the use of multiple agents was implicated in 9% of cases.
Looking at outcomes, the researchers reported that DILI was mild in 35 patients (36%), moderate in 55 patients (58%), and severe in 5 patients (5%); there was 1 death, in an 82-year-old patient.
Finally, the median duration from diagnosis of DILI to the normalization of liver enzymes was 64 days, and 7% still had abnormal liver tests 6 months after DILI diagnosis.
According to the authors, the only previously published population-based study, done in France, found an annual crude incidence rate of 13.9 cases per 100,000 inhabitants per year (Hepatology 2002;36:451-5).
They conceded that their rate is somewhat higher; however, "the French study provided no information about the patients at risk for DILI because information about drug consumption was not available," they wrote.
The authors stated that the study was funded by a grant from the National University Hospital of Iceland Research Fund; they disclosed no individual financial conflicts of interest.
The crude incidence of drug-induced liver injury is roughly 19.1 cases per 100,000 inhabitants, with amoxicillin-clavulanate the most commonly implicated agent.
That’s according to the second published population-based cohort study of drug-induced liver injury (DILI), wrote Dr. Einar S. Björnsson. The study was published in the June issue of Gastroenterology.
Dr. Björnsson, of the University of Iceland, and colleagues looked at all patients aged older than 15 years hospitalized for liver disease with suspected DILI, plus outpatients at the National University Hospital of Iceland, and all those seen in private practice between March 1, 2010, and Feb. 29, 2012.
Source: American Gastroenterological Association
According to the authors, "In Iceland, every citizen is issued a specific personal identification number that is, among other things, connected to a nationwide pharmaceutical database on outpatient prescriptions."
Therefore, "The study examined the Icelandic Medicines Registry records of prescriptions for all drugs associated with DILI that had at least a possible causal relationship" according to the Roussel Uclaf Causality Assessment Method.
DILI was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal, and/or alkaline phosphatase (ALP) levels greater than two times the upper limit of normal.
Acetaminophen toxicity cases were excluded, though patients with preexisting chronic liver injury were not, if they were considered to have developed superimposed DILI on top of their baseline liver enzyme values.
The authors found that over the study period there were 96 cases eligible for inclusion, including 49 cases in the first year and 47 in the second. That translated into a crude annual incidence during the study period of 19.1 cases per 100,000 inhabitants.
Roughly half were female (56%), and the median age was 55 years (range, 16-91 years).
Looking at the clinical characteristics of the cohort, the authors calculated that only 27% of patients developed jaundice, while 10% of patients complained of rash and 6% of fever. Four of the patients had preexisting liver disease.
Overall, liver injury was judged to be due to a single prescription medication in 75% of cases, most commonly amoxicillin-clavulanate (22%), followed by diclofenac (6%), azathioprine (4%) infliximab (4%), and nitrofurantoin (4%).
By tying the injury to Iceland’s prescription drug database, that meant an incidence of DILI among outpatients of 1 per 133 filled azathioprine prescriptions and 1 in 2,350 amoxicillin-clavulanate users; among inpatients, the incidence of injury attributed to amoxicillin-clavulanate was 1 per 729 patients.
By drug classes, after antibiotics, immunosuppressants were found to be commonly associated with DILI (10%), followed by psychotropic drugs, which accounted for 7% of cases, and then nonsteroidal anti-inflammatory drugs, at 6%, "with diclofenac as the only agent."
Single-drug antineoplastic agents were the causes of DILI in 5% of the cohort, and lipid-lowering agents were the cause in just 3.1% of patients (atorvastatin, n = 2; simvastatin, n = 1).
After injuries due to a single agent, dietary supplements were assumed to be the culprit in 16% of cases, and the use of multiple agents was implicated in 9% of cases.
Looking at outcomes, the researchers reported that DILI was mild in 35 patients (36%), moderate in 55 patients (58%), and severe in 5 patients (5%); there was 1 death, in an 82-year-old patient.
Finally, the median duration from diagnosis of DILI to the normalization of liver enzymes was 64 days, and 7% still had abnormal liver tests 6 months after DILI diagnosis.
According to the authors, the only previously published population-based study, done in France, found an annual crude incidence rate of 13.9 cases per 100,000 inhabitants per year (Hepatology 2002;36:451-5).
They conceded that their rate is somewhat higher; however, "the French study provided no information about the patients at risk for DILI because information about drug consumption was not available," they wrote.
The authors stated that the study was funded by a grant from the National University Hospital of Iceland Research Fund; they disclosed no individual financial conflicts of interest.
FROM GASTROENTEROLOGY
Major finding: Drug-induced liver injury has an incidence of 19.1 per 100,000 persons, with the incidence per outpatient users of amoxicillin-clavulanate at 1 per 2,350.
Data source: A population-based cohort study of 251,000 Icelanders.
Disclosures: The authors stated that the study was funded by a grant from the National University Hospital of Iceland Research Fund; they disclosed no individual conflicts.
Gluten-free diet may hold benefit in IBS
A gluten-free diet reduced stool frequency as well as small bowel permeability in irritable bowel syndrome patients without celiac disease.
The findings, published in the May issue of Gastroenterology, "support the need for further clinical intervention studies to evaluate the clinical effects of gluten withdrawal in patients with diarrhea-predominant IBS," reported Dr. Maria I. Vazquez-Roque and her colleagues.
Dr. Vasquez-Roque, of the Mayo Clinic’s Clinical Enteric Neuroscience Translational and Epidemiological Research Program, in Rochester, Minn., and her colleagues recruited 45 subjects (43 women) from a database of more than 800 patients with irritable bowel syndrome who had been evaluated at the Mayo Clinic.
All patients had diarrhea-predominant IBS (IBS-D), were not on a gluten-free diet prior to the study, and did not have celiac disease.
They were randomized to either a gluten-free diet or a gluten-containing diet for 28 days. Patients’ meals and snacks were ingested or prepared in the Mayo Clinical Research Unit, and study participants were asked to eat only the foods provided by the study dietitians during the entire study period, the authors wrote. Dietitians assessed diet compliance using direct questioning of participants.
After 28 days of the study, the investigators looked at several clinical and histologic markers.
First, they tallied stool frequency, and found that patients on the gluten-containing diet had more stools per day than gluten-free patients did (P = .04), with a 95% confidence interval for the absolute difference between number of stools per day at –0.652 to –0.015 (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.049]).
"While the absolute difference in stool frequency is small, it is important to appreciate that this increased frequency is on a background of the typical increase in stool frequency (average 2.6 bowel movements/day at baseline) and consistency in patients with IBS-D," the authors wrote.
This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (95% CI, –1.005 to –0.092; P = .019), they added.
Next, the investigators looked at small bowel permeability.
They found increased small bowel permeability with gluten-containing diet patients relative to their gluten-free counterparts, based on both cumulative mannitol excretion levels and lactulose:mannitol ratio. Similarly, this effect was more pronounced in HLA-DQ2 or 8 positive patients.
"While the clinical significance of these changes in permeability is not demonstrated in the current study, the abundant experimental evidence from the published literature is that increased mucosal permeability enhances inflammation and leads to increased sensitivity," they wrote.
Finally, the authors looked at tight-junction mRNA expression.
"Alterations in intestinal permeability and jejunal mucosal tight junction (TJ) signaling have been described in IBS-D, including postinfectious IBS-D," they wrote.
They found that expressions of ZO-1, occludin, and claudin-1 mRNA in colonic mucosa were significantly lower with the gluten-containing diet, compared with the gluten-free patients, particularly in subjects with HLA-DQ2 or 8 positive status.
There were no significant variations in tight junction signaling in the small bowel mucosa.
The authors conceded several limitations to their study. For one, it "did not evaluate effects of gluten on the microbiome, afferent functions, or cytokine expression in the mucosal biopsies from patients before and after the interventions. These would be interesting parameters to include in future studies," they wrote.
Additionally, "our study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed."
Nevertheless, "our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS," they concluded.
The researchers disclosed receiving funding for this study from the National Institutes of Health. One investigator also disclosed having received grants from Alba Therapeutics, maker of the drug larazotide, used in celiac disease.
Recently, we have seen the emergence of
nonceliac gluten sensitivity as a distinct clinical entity. It is as if the medical
community has caught up to the food industry and the patients because there has
been an explosion in the availability of gluten-free foods and some patients,
without celiac disease, have been telling us they feel better when gluten has
been withdrawn from their diet.
A recent study from Australia demonstrated in a double-blind,
randomized study of a gluten-containing diet versus a gluten-free diet
that individuals with irritable bowel syndrome (IBS) who had self-selected as
being gluten sensitive experienced more gastrointestinal symptoms and fatigue
when exposed to the gluten-containing diet.
The investigators from the Mayo Clinic in Rochester,
Minn. extended these studies to patients with diarrhea-predominant
IBS who had not self-selected as being gluten sensitive. They demonstrated that
the gluten-free diet reduced stool frequency and small bowel permeability and
that the effect was most prominent in those who possessed the celiac disease at
risk genes, HLA DQ2 and DQ8.
Gluten is not fully digested by our digestive system,
unlike meat protein. The large amino acid molecules that remain after digestion
appear responsible for the development of celiac disease in some individuals
who are HLA DQ2 or -8 positive. It now appears that gluten (or other
proteins found in wheat) may induce changes that result in symptoms in patients
labeled as having IBS.
So those that have already self-diagnosed as being
gluten sensitive may in fact just be the tip of the iceberg of gluten
sensitivity.
Peter H.R. Green, M.D., is the Director of
the Celiac Disease Center, Columbia University, New York, and professor of
clinical medicine at the College of Physicians and Surgeons. Dr. Green is on
the scientific advisory boards for Alvine Pharmaceuticals and ImmusanT.
Recently, we have seen the emergence of
nonceliac gluten sensitivity as a distinct clinical entity. It is as if the medical
community has caught up to the food industry and the patients because there has
been an explosion in the availability of gluten-free foods and some patients,
without celiac disease, have been telling us they feel better when gluten has
been withdrawn from their diet.
A recent study from Australia demonstrated in a double-blind,
randomized study of a gluten-containing diet versus a gluten-free diet
that individuals with irritable bowel syndrome (IBS) who had self-selected as
being gluten sensitive experienced more gastrointestinal symptoms and fatigue
when exposed to the gluten-containing diet.
The investigators from the Mayo Clinic in Rochester,
Minn. extended these studies to patients with diarrhea-predominant
IBS who had not self-selected as being gluten sensitive. They demonstrated that
the gluten-free diet reduced stool frequency and small bowel permeability and
that the effect was most prominent in those who possessed the celiac disease at
risk genes, HLA DQ2 and DQ8.
Gluten is not fully digested by our digestive system,
unlike meat protein. The large amino acid molecules that remain after digestion
appear responsible for the development of celiac disease in some individuals
who are HLA DQ2 or -8 positive. It now appears that gluten (or other
proteins found in wheat) may induce changes that result in symptoms in patients
labeled as having IBS.
So those that have already self-diagnosed as being
gluten sensitive may in fact just be the tip of the iceberg of gluten
sensitivity.
Peter H.R. Green, M.D., is the Director of
the Celiac Disease Center, Columbia University, New York, and professor of
clinical medicine at the College of Physicians and Surgeons. Dr. Green is on
the scientific advisory boards for Alvine Pharmaceuticals and ImmusanT.
Recently, we have seen the emergence of
nonceliac gluten sensitivity as a distinct clinical entity. It is as if the medical
community has caught up to the food industry and the patients because there has
been an explosion in the availability of gluten-free foods and some patients,
without celiac disease, have been telling us they feel better when gluten has
been withdrawn from their diet.
A recent study from Australia demonstrated in a double-blind,
randomized study of a gluten-containing diet versus a gluten-free diet
that individuals with irritable bowel syndrome (IBS) who had self-selected as
being gluten sensitive experienced more gastrointestinal symptoms and fatigue
when exposed to the gluten-containing diet.
The investigators from the Mayo Clinic in Rochester,
Minn. extended these studies to patients with diarrhea-predominant
IBS who had not self-selected as being gluten sensitive. They demonstrated that
the gluten-free diet reduced stool frequency and small bowel permeability and
that the effect was most prominent in those who possessed the celiac disease at
risk genes, HLA DQ2 and DQ8.
Gluten is not fully digested by our digestive system,
unlike meat protein. The large amino acid molecules that remain after digestion
appear responsible for the development of celiac disease in some individuals
who are HLA DQ2 or -8 positive. It now appears that gluten (or other
proteins found in wheat) may induce changes that result in symptoms in patients
labeled as having IBS.
So those that have already self-diagnosed as being
gluten sensitive may in fact just be the tip of the iceberg of gluten
sensitivity.
Peter H.R. Green, M.D., is the Director of
the Celiac Disease Center, Columbia University, New York, and professor of
clinical medicine at the College of Physicians and Surgeons. Dr. Green is on
the scientific advisory boards for Alvine Pharmaceuticals and ImmusanT.
A gluten-free diet reduced stool frequency as well as small bowel permeability in irritable bowel syndrome patients without celiac disease.
The findings, published in the May issue of Gastroenterology, "support the need for further clinical intervention studies to evaluate the clinical effects of gluten withdrawal in patients with diarrhea-predominant IBS," reported Dr. Maria I. Vazquez-Roque and her colleagues.
Dr. Vasquez-Roque, of the Mayo Clinic’s Clinical Enteric Neuroscience Translational and Epidemiological Research Program, in Rochester, Minn., and her colleagues recruited 45 subjects (43 women) from a database of more than 800 patients with irritable bowel syndrome who had been evaluated at the Mayo Clinic.
All patients had diarrhea-predominant IBS (IBS-D), were not on a gluten-free diet prior to the study, and did not have celiac disease.
They were randomized to either a gluten-free diet or a gluten-containing diet for 28 days. Patients’ meals and snacks were ingested or prepared in the Mayo Clinical Research Unit, and study participants were asked to eat only the foods provided by the study dietitians during the entire study period, the authors wrote. Dietitians assessed diet compliance using direct questioning of participants.
After 28 days of the study, the investigators looked at several clinical and histologic markers.
First, they tallied stool frequency, and found that patients on the gluten-containing diet had more stools per day than gluten-free patients did (P = .04), with a 95% confidence interval for the absolute difference between number of stools per day at –0.652 to –0.015 (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.049]).
"While the absolute difference in stool frequency is small, it is important to appreciate that this increased frequency is on a background of the typical increase in stool frequency (average 2.6 bowel movements/day at baseline) and consistency in patients with IBS-D," the authors wrote.
This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (95% CI, –1.005 to –0.092; P = .019), they added.
Next, the investigators looked at small bowel permeability.
They found increased small bowel permeability with gluten-containing diet patients relative to their gluten-free counterparts, based on both cumulative mannitol excretion levels and lactulose:mannitol ratio. Similarly, this effect was more pronounced in HLA-DQ2 or 8 positive patients.
"While the clinical significance of these changes in permeability is not demonstrated in the current study, the abundant experimental evidence from the published literature is that increased mucosal permeability enhances inflammation and leads to increased sensitivity," they wrote.
Finally, the authors looked at tight-junction mRNA expression.
"Alterations in intestinal permeability and jejunal mucosal tight junction (TJ) signaling have been described in IBS-D, including postinfectious IBS-D," they wrote.
They found that expressions of ZO-1, occludin, and claudin-1 mRNA in colonic mucosa were significantly lower with the gluten-containing diet, compared with the gluten-free patients, particularly in subjects with HLA-DQ2 or 8 positive status.
There were no significant variations in tight junction signaling in the small bowel mucosa.
The authors conceded several limitations to their study. For one, it "did not evaluate effects of gluten on the microbiome, afferent functions, or cytokine expression in the mucosal biopsies from patients before and after the interventions. These would be interesting parameters to include in future studies," they wrote.
Additionally, "our study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed."
Nevertheless, "our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS," they concluded.
The researchers disclosed receiving funding for this study from the National Institutes of Health. One investigator also disclosed having received grants from Alba Therapeutics, maker of the drug larazotide, used in celiac disease.
A gluten-free diet reduced stool frequency as well as small bowel permeability in irritable bowel syndrome patients without celiac disease.
The findings, published in the May issue of Gastroenterology, "support the need for further clinical intervention studies to evaluate the clinical effects of gluten withdrawal in patients with diarrhea-predominant IBS," reported Dr. Maria I. Vazquez-Roque and her colleagues.
Dr. Vasquez-Roque, of the Mayo Clinic’s Clinical Enteric Neuroscience Translational and Epidemiological Research Program, in Rochester, Minn., and her colleagues recruited 45 subjects (43 women) from a database of more than 800 patients with irritable bowel syndrome who had been evaluated at the Mayo Clinic.
All patients had diarrhea-predominant IBS (IBS-D), were not on a gluten-free diet prior to the study, and did not have celiac disease.
They were randomized to either a gluten-free diet or a gluten-containing diet for 28 days. Patients’ meals and snacks were ingested or prepared in the Mayo Clinical Research Unit, and study participants were asked to eat only the foods provided by the study dietitians during the entire study period, the authors wrote. Dietitians assessed diet compliance using direct questioning of participants.
After 28 days of the study, the investigators looked at several clinical and histologic markers.
First, they tallied stool frequency, and found that patients on the gluten-containing diet had more stools per day than gluten-free patients did (P = .04), with a 95% confidence interval for the absolute difference between number of stools per day at –0.652 to –0.015 (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.049]).
"While the absolute difference in stool frequency is small, it is important to appreciate that this increased frequency is on a background of the typical increase in stool frequency (average 2.6 bowel movements/day at baseline) and consistency in patients with IBS-D," the authors wrote.
This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (95% CI, –1.005 to –0.092; P = .019), they added.
Next, the investigators looked at small bowel permeability.
They found increased small bowel permeability with gluten-containing diet patients relative to their gluten-free counterparts, based on both cumulative mannitol excretion levels and lactulose:mannitol ratio. Similarly, this effect was more pronounced in HLA-DQ2 or 8 positive patients.
"While the clinical significance of these changes in permeability is not demonstrated in the current study, the abundant experimental evidence from the published literature is that increased mucosal permeability enhances inflammation and leads to increased sensitivity," they wrote.
Finally, the authors looked at tight-junction mRNA expression.
"Alterations in intestinal permeability and jejunal mucosal tight junction (TJ) signaling have been described in IBS-D, including postinfectious IBS-D," they wrote.
They found that expressions of ZO-1, occludin, and claudin-1 mRNA in colonic mucosa were significantly lower with the gluten-containing diet, compared with the gluten-free patients, particularly in subjects with HLA-DQ2 or 8 positive status.
There were no significant variations in tight junction signaling in the small bowel mucosa.
The authors conceded several limitations to their study. For one, it "did not evaluate effects of gluten on the microbiome, afferent functions, or cytokine expression in the mucosal biopsies from patients before and after the interventions. These would be interesting parameters to include in future studies," they wrote.
Additionally, "our study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed."
Nevertheless, "our data provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS," they concluded.
The researchers disclosed receiving funding for this study from the National Institutes of Health. One investigator also disclosed having received grants from Alba Therapeutics, maker of the drug larazotide, used in celiac disease.
FROM GASTROENTEROLOGY
Major finding: Irritable bowel syndrome patients on a gluten-free diet had fewer bowel movements per day than did gluten-consuming counterparts (P = .04).
Data source: A 4-week trial of 45 patients with diarrhea-predominant irritable bowel syndrome, randomized to a gluten-free or gluten-containing diet.
Disclosures: The researchers disclosed receiving funding for this study from the National Institutes of Health. One investigator also disclosed having received grants from Alba Therapeutics, maker of the drug larazotide, used in celiac disease.
Consider steroids in anti-TNF liver injury
Patients with liver injury secondary to anti–tumor necrosis factor–alpha agents often exhibit histological changes similar to those seen in spontaneous autoimmune hepatitis, wrote Dr. Marwan Ghabril and his colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology.
The finding comes from a review seeking to characterize the presentation, injury pattern, course of illness, and treatment of anti-TNF agent–induced liver injury, which Dr. Ghabril, of Indiana University in Indianapolis, said "may be severe and prolonged."
To that end, he and his colleagues studied six patients from the U.S. Drug-Induced Liver Injury Network (DILIN) database who had liver damage that was likely secondary to anti-TNFs, according to DILIN criteria.
Additionally, 28 cases were culled from a literature review of the PubMed database using the search terms "hepatotoxicity," "liver injury," "tumor necrosis factor," and the generic names of all TNF-alpha antagonists.
Among all patients, infliximab was most commonly the offending agent, followed by etanercept and adalimumab; no cases were attributed to natalizumab, golimumab, or certolizumab.
Diseases for which the anti-TNFs were prescribed included ankylosing spondylitis, Crohn’s disease, chronic ulcerative colitis, juvenile inflammatory arthritis, psoriatic arthritis, psoriasis, and rheumatoid arthritis.
First, Dr. Ghabril looked at the six patients from the DILIN database. Among these patients, the median duration of drug use before onset of liver injury was 16 weeks (range, 2-52 weeks).
"At presentation, half had jaundice, half had nausea, but only one had fever and none had immuno-allergic features of skin rash or eosinophilia," wrote the authors.
Only one of these patients developed significantly impaired coagulation, with an INR of 3.5, and none of the DILIN patients developed ascites or other signs of hepatic failure, they added.
The peak ALT ranged from 384 to 1,687 U/L, and the peak bilirubin from 1.5 to 27.7 mg/dL.
"Five of the six patients were treated with corticosteroids. One patient had a protracted illness, but all ultimately recovered and could be withdrawn from corticosteroid therapy without recurrence," they wrote.
Next, the authors turned their attention to the PubMed cases.
"Peak serum ALT ranged from 140 to 2,250 U/L and bilirubin from normal to 27.7 mg/dL," the authors reported.
Most patients (n = 22) had autoimmune serological markers and/or histological features at some point during the clinical course, they found.
Twelve patients stopped the drug and initiated corticosteroid therapy, oral or parenteral; all recovered. The rest improved after discontinuation of the anti-TNF, without steroid treatment, except for one patient who had underlying cirrhosis and required liver transplantation.
Notably, several patients were able to continue anti-TNF treatment with another agent without further incident, the authors wrote. Indeed, "three tolerated treatment with etanercept without recurrence of liver injury after cessation of infliximab or adalimumab. Two did well with adalimumab after [drug-induced liver injury] associated with infliximab, and one was successfully switched from adalimumab to abatacept."
Finally, the investigators contrasted patients with serological or histological autoimmune features with patients who lacked any autoimmune characteristics.
The autoimmune patients tended to have a longer latency period. The median period after the drug was initiated but before liver injury was noted was 16 weeks for the autoimmune patients versus 10 weeks for the nonautoimmune patients (P = .17). The autoimmune patients also had a higher peak ALT (median 784 vs. 528; P = .03).
"The mechanism by which the TNF-alpha antagonists lead to drug-induced liver injury is unknown," the authors wrote.
"Because the injury can occur after only one infusion, dose-dependent toxicity is unlikely. Unpredictable, idiosyncratic drug-induced liver injury seems most likely, as in this series no patients had clinical evidence of a rash or eosinophilia, and only one presented with fever."
"Further studies are needed to ascertain whether genetic or other markers of the hepatotoxicity associated with TNF-alpha antagonists can be identified," they said.
The DILIN database is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported having no conflicts of interest.
Patients with liver injury secondary to anti–tumor necrosis factor–alpha agents often exhibit histological changes similar to those seen in spontaneous autoimmune hepatitis, wrote Dr. Marwan Ghabril and his colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology.
The finding comes from a review seeking to characterize the presentation, injury pattern, course of illness, and treatment of anti-TNF agent–induced liver injury, which Dr. Ghabril, of Indiana University in Indianapolis, said "may be severe and prolonged."
To that end, he and his colleagues studied six patients from the U.S. Drug-Induced Liver Injury Network (DILIN) database who had liver damage that was likely secondary to anti-TNFs, according to DILIN criteria.
Additionally, 28 cases were culled from a literature review of the PubMed database using the search terms "hepatotoxicity," "liver injury," "tumor necrosis factor," and the generic names of all TNF-alpha antagonists.
Among all patients, infliximab was most commonly the offending agent, followed by etanercept and adalimumab; no cases were attributed to natalizumab, golimumab, or certolizumab.
Diseases for which the anti-TNFs were prescribed included ankylosing spondylitis, Crohn’s disease, chronic ulcerative colitis, juvenile inflammatory arthritis, psoriatic arthritis, psoriasis, and rheumatoid arthritis.
First, Dr. Ghabril looked at the six patients from the DILIN database. Among these patients, the median duration of drug use before onset of liver injury was 16 weeks (range, 2-52 weeks).
"At presentation, half had jaundice, half had nausea, but only one had fever and none had immuno-allergic features of skin rash or eosinophilia," wrote the authors.
Only one of these patients developed significantly impaired coagulation, with an INR of 3.5, and none of the DILIN patients developed ascites or other signs of hepatic failure, they added.
The peak ALT ranged from 384 to 1,687 U/L, and the peak bilirubin from 1.5 to 27.7 mg/dL.
"Five of the six patients were treated with corticosteroids. One patient had a protracted illness, but all ultimately recovered and could be withdrawn from corticosteroid therapy without recurrence," they wrote.
Next, the authors turned their attention to the PubMed cases.
"Peak serum ALT ranged from 140 to 2,250 U/L and bilirubin from normal to 27.7 mg/dL," the authors reported.
Most patients (n = 22) had autoimmune serological markers and/or histological features at some point during the clinical course, they found.
Twelve patients stopped the drug and initiated corticosteroid therapy, oral or parenteral; all recovered. The rest improved after discontinuation of the anti-TNF, without steroid treatment, except for one patient who had underlying cirrhosis and required liver transplantation.
Notably, several patients were able to continue anti-TNF treatment with another agent without further incident, the authors wrote. Indeed, "three tolerated treatment with etanercept without recurrence of liver injury after cessation of infliximab or adalimumab. Two did well with adalimumab after [drug-induced liver injury] associated with infliximab, and one was successfully switched from adalimumab to abatacept."
Finally, the investigators contrasted patients with serological or histological autoimmune features with patients who lacked any autoimmune characteristics.
The autoimmune patients tended to have a longer latency period. The median period after the drug was initiated but before liver injury was noted was 16 weeks for the autoimmune patients versus 10 weeks for the nonautoimmune patients (P = .17). The autoimmune patients also had a higher peak ALT (median 784 vs. 528; P = .03).
"The mechanism by which the TNF-alpha antagonists lead to drug-induced liver injury is unknown," the authors wrote.
"Because the injury can occur after only one infusion, dose-dependent toxicity is unlikely. Unpredictable, idiosyncratic drug-induced liver injury seems most likely, as in this series no patients had clinical evidence of a rash or eosinophilia, and only one presented with fever."
"Further studies are needed to ascertain whether genetic or other markers of the hepatotoxicity associated with TNF-alpha antagonists can be identified," they said.
The DILIN database is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported having no conflicts of interest.
Patients with liver injury secondary to anti–tumor necrosis factor–alpha agents often exhibit histological changes similar to those seen in spontaneous autoimmune hepatitis, wrote Dr. Marwan Ghabril and his colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology.
The finding comes from a review seeking to characterize the presentation, injury pattern, course of illness, and treatment of anti-TNF agent–induced liver injury, which Dr. Ghabril, of Indiana University in Indianapolis, said "may be severe and prolonged."
To that end, he and his colleagues studied six patients from the U.S. Drug-Induced Liver Injury Network (DILIN) database who had liver damage that was likely secondary to anti-TNFs, according to DILIN criteria.
Additionally, 28 cases were culled from a literature review of the PubMed database using the search terms "hepatotoxicity," "liver injury," "tumor necrosis factor," and the generic names of all TNF-alpha antagonists.
Among all patients, infliximab was most commonly the offending agent, followed by etanercept and adalimumab; no cases were attributed to natalizumab, golimumab, or certolizumab.
Diseases for which the anti-TNFs were prescribed included ankylosing spondylitis, Crohn’s disease, chronic ulcerative colitis, juvenile inflammatory arthritis, psoriatic arthritis, psoriasis, and rheumatoid arthritis.
First, Dr. Ghabril looked at the six patients from the DILIN database. Among these patients, the median duration of drug use before onset of liver injury was 16 weeks (range, 2-52 weeks).
"At presentation, half had jaundice, half had nausea, but only one had fever and none had immuno-allergic features of skin rash or eosinophilia," wrote the authors.
Only one of these patients developed significantly impaired coagulation, with an INR of 3.5, and none of the DILIN patients developed ascites or other signs of hepatic failure, they added.
The peak ALT ranged from 384 to 1,687 U/L, and the peak bilirubin from 1.5 to 27.7 mg/dL.
"Five of the six patients were treated with corticosteroids. One patient had a protracted illness, but all ultimately recovered and could be withdrawn from corticosteroid therapy without recurrence," they wrote.
Next, the authors turned their attention to the PubMed cases.
"Peak serum ALT ranged from 140 to 2,250 U/L and bilirubin from normal to 27.7 mg/dL," the authors reported.
Most patients (n = 22) had autoimmune serological markers and/or histological features at some point during the clinical course, they found.
Twelve patients stopped the drug and initiated corticosteroid therapy, oral or parenteral; all recovered. The rest improved after discontinuation of the anti-TNF, without steroid treatment, except for one patient who had underlying cirrhosis and required liver transplantation.
Notably, several patients were able to continue anti-TNF treatment with another agent without further incident, the authors wrote. Indeed, "three tolerated treatment with etanercept without recurrence of liver injury after cessation of infliximab or adalimumab. Two did well with adalimumab after [drug-induced liver injury] associated with infliximab, and one was successfully switched from adalimumab to abatacept."
Finally, the investigators contrasted patients with serological or histological autoimmune features with patients who lacked any autoimmune characteristics.
The autoimmune patients tended to have a longer latency period. The median period after the drug was initiated but before liver injury was noted was 16 weeks for the autoimmune patients versus 10 weeks for the nonautoimmune patients (P = .17). The autoimmune patients also had a higher peak ALT (median 784 vs. 528; P = .03).
"The mechanism by which the TNF-alpha antagonists lead to drug-induced liver injury is unknown," the authors wrote.
"Because the injury can occur after only one infusion, dose-dependent toxicity is unlikely. Unpredictable, idiosyncratic drug-induced liver injury seems most likely, as in this series no patients had clinical evidence of a rash or eosinophilia, and only one presented with fever."
"Further studies are needed to ascertain whether genetic or other markers of the hepatotoxicity associated with TNF-alpha antagonists can be identified," they said.
The DILIN database is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major finding: Peak ALT levels ranged from 140 to 2,250 U/L among patients with liver injury secondary to tumor necrosis factor–alpha antagonists.
Data source: An analysis of 34 cases of liver injury from the literature and a liver-injury database.
Disclosures: The DILIN database is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported having no conflicts of interest.
Celiac disease patients protected from type 2 diabetes
Patients with celiac disease have a significantly lower prevalence of type 2 diabetes than do matched controls without celiac disease and the general population, Dr. Toufic A. Kabbani and his colleagues reported in a study published in the May issue of Gastroenterology.
Moreover, "the possible explanation that the lower rate of NIDDM [non–insulin-dependent diabetes mellitus] in individuals with celiac disease is due to different body mass index distribution is not supported by our study data, as the lower prevalence of NIDDM in celiac disease remains significant after controlling for BMI," they added.
| Source: American Gastroenterological Association |
Dr. Kabbani, of the Celiac Center at the Beth Israel Deaconess Medical Center, Boston, looked at the records of 840 adults with biopsy-proven celiac disease to determine the prevalence of type 2 diabetes or metabolic syndrome. The data were culled from the Celiac Center’s database.
Patients were matched by age, sex, and ethnicity to 840 controls without celiac disease chosen at random from a list of adults presenting to their primary medical provider for an annual checkup.
Patients were also compared with a cohort from the National Health and Nutrition Examination Survey (NHANES) population for reference.
According to the authors, both the celiac disease cohort and their matched counterparts were mainly white (88.9%) and female (72.5%).
Overall, 26 patients in the celiac group had type 2 diabetes (3.1%), compared with 81 controls (9.6%, P less than .0001) (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.033]).
The prevalence of type 2 diabetes among celiac patients was also significantly lower than the estimated national prevalence derived from NHANES, which was 9.8% (P less than .0001).
Similarly, celiac patients recorded a significantly lower prevalence of metabolic syndrome than did controls (3.5% vs. 12.7%, P less than 0.0001).
Next, the authors conducted a multivariate analysis in which they controlled for BMI and smoking among celiac disease patients. The significantly negative association between celiac disease and type 2 diabetes persisted, with an odds ratio for diabetes among celiac patients of 0.49 (95% confidence interval, 0.29-0.83; P = .008).
"The mechanisms by which individuals with celiac disease are protected from NIDDM and metabolic syndrome are not clear at this time; however, possible explanations include altered pancreatic function, impaired nutrient absorption, and changes in gastrointestinal endocrine function," postulated the authors.
Alternatively, they wrote: "Tissue transglutaminase (tTG) drives inflammation in celiac disease via the down-regulation of peroxisome proliferator–activated receptor gamma (PPARG). On the other hand, PPARG up-regulation has been implicated in [type 2 diabetes] susceptibility.
"Therefore, the down-regulation of PPARG in celiac disease may be implicated in decreased risk of [type 2 diabetes]," the authors said.
Dr. Kabbani conceded that this study had several limitations. For one, most patients did not have an available waist circumference measurement, which is a criterion for metabolic syndrome, according to the International Diabetes Federation. As a proxy, the authors used a BMI of greater than 30 kg/m2. "While this might have affected the prevalence of metabolic syndrome in our study, we expect its impact on our analysis to be minor," they wrote.
Additionally, most celiac patients who started a gluten-free diet did not have endoscopic follow-up to assess intestinal healing.
However, "91.2% of these subjects had clinical improvement as well as normalization of their tTG titers, which increases the likelihood of histological improvement or remission."
None of the authors disclosed any financial conflicts relevant to this study. They disclosed no outside funding.
Patients with celiac disease have a significantly lower prevalence of type 2 diabetes than do matched controls without celiac disease and the general population, Dr. Toufic A. Kabbani and his colleagues reported in a study published in the May issue of Gastroenterology.
Moreover, "the possible explanation that the lower rate of NIDDM [non–insulin-dependent diabetes mellitus] in individuals with celiac disease is due to different body mass index distribution is not supported by our study data, as the lower prevalence of NIDDM in celiac disease remains significant after controlling for BMI," they added.
| Source: American Gastroenterological Association |
Dr. Kabbani, of the Celiac Center at the Beth Israel Deaconess Medical Center, Boston, looked at the records of 840 adults with biopsy-proven celiac disease to determine the prevalence of type 2 diabetes or metabolic syndrome. The data were culled from the Celiac Center’s database.
Patients were matched by age, sex, and ethnicity to 840 controls without celiac disease chosen at random from a list of adults presenting to their primary medical provider for an annual checkup.
Patients were also compared with a cohort from the National Health and Nutrition Examination Survey (NHANES) population for reference.
According to the authors, both the celiac disease cohort and their matched counterparts were mainly white (88.9%) and female (72.5%).
Overall, 26 patients in the celiac group had type 2 diabetes (3.1%), compared with 81 controls (9.6%, P less than .0001) (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.033]).
The prevalence of type 2 diabetes among celiac patients was also significantly lower than the estimated national prevalence derived from NHANES, which was 9.8% (P less than .0001).
Similarly, celiac patients recorded a significantly lower prevalence of metabolic syndrome than did controls (3.5% vs. 12.7%, P less than 0.0001).
Next, the authors conducted a multivariate analysis in which they controlled for BMI and smoking among celiac disease patients. The significantly negative association between celiac disease and type 2 diabetes persisted, with an odds ratio for diabetes among celiac patients of 0.49 (95% confidence interval, 0.29-0.83; P = .008).
"The mechanisms by which individuals with celiac disease are protected from NIDDM and metabolic syndrome are not clear at this time; however, possible explanations include altered pancreatic function, impaired nutrient absorption, and changes in gastrointestinal endocrine function," postulated the authors.
Alternatively, they wrote: "Tissue transglutaminase (tTG) drives inflammation in celiac disease via the down-regulation of peroxisome proliferator–activated receptor gamma (PPARG). On the other hand, PPARG up-regulation has been implicated in [type 2 diabetes] susceptibility.
"Therefore, the down-regulation of PPARG in celiac disease may be implicated in decreased risk of [type 2 diabetes]," the authors said.
Dr. Kabbani conceded that this study had several limitations. For one, most patients did not have an available waist circumference measurement, which is a criterion for metabolic syndrome, according to the International Diabetes Federation. As a proxy, the authors used a BMI of greater than 30 kg/m2. "While this might have affected the prevalence of metabolic syndrome in our study, we expect its impact on our analysis to be minor," they wrote.
Additionally, most celiac patients who started a gluten-free diet did not have endoscopic follow-up to assess intestinal healing.
However, "91.2% of these subjects had clinical improvement as well as normalization of their tTG titers, which increases the likelihood of histological improvement or remission."
None of the authors disclosed any financial conflicts relevant to this study. They disclosed no outside funding.
Patients with celiac disease have a significantly lower prevalence of type 2 diabetes than do matched controls without celiac disease and the general population, Dr. Toufic A. Kabbani and his colleagues reported in a study published in the May issue of Gastroenterology.
Moreover, "the possible explanation that the lower rate of NIDDM [non–insulin-dependent diabetes mellitus] in individuals with celiac disease is due to different body mass index distribution is not supported by our study data, as the lower prevalence of NIDDM in celiac disease remains significant after controlling for BMI," they added.
| Source: American Gastroenterological Association |
Dr. Kabbani, of the Celiac Center at the Beth Israel Deaconess Medical Center, Boston, looked at the records of 840 adults with biopsy-proven celiac disease to determine the prevalence of type 2 diabetes or metabolic syndrome. The data were culled from the Celiac Center’s database.
Patients were matched by age, sex, and ethnicity to 840 controls without celiac disease chosen at random from a list of adults presenting to their primary medical provider for an annual checkup.
Patients were also compared with a cohort from the National Health and Nutrition Examination Survey (NHANES) population for reference.
According to the authors, both the celiac disease cohort and their matched counterparts were mainly white (88.9%) and female (72.5%).
Overall, 26 patients in the celiac group had type 2 diabetes (3.1%), compared with 81 controls (9.6%, P less than .0001) (Gastroenterology 2013 Jan. 28 [doi: 10.1053/j.gastro.2013.01.033]).
The prevalence of type 2 diabetes among celiac patients was also significantly lower than the estimated national prevalence derived from NHANES, which was 9.8% (P less than .0001).
Similarly, celiac patients recorded a significantly lower prevalence of metabolic syndrome than did controls (3.5% vs. 12.7%, P less than 0.0001).
Next, the authors conducted a multivariate analysis in which they controlled for BMI and smoking among celiac disease patients. The significantly negative association between celiac disease and type 2 diabetes persisted, with an odds ratio for diabetes among celiac patients of 0.49 (95% confidence interval, 0.29-0.83; P = .008).
"The mechanisms by which individuals with celiac disease are protected from NIDDM and metabolic syndrome are not clear at this time; however, possible explanations include altered pancreatic function, impaired nutrient absorption, and changes in gastrointestinal endocrine function," postulated the authors.
Alternatively, they wrote: "Tissue transglutaminase (tTG) drives inflammation in celiac disease via the down-regulation of peroxisome proliferator–activated receptor gamma (PPARG). On the other hand, PPARG up-regulation has been implicated in [type 2 diabetes] susceptibility.
"Therefore, the down-regulation of PPARG in celiac disease may be implicated in decreased risk of [type 2 diabetes]," the authors said.
Dr. Kabbani conceded that this study had several limitations. For one, most patients did not have an available waist circumference measurement, which is a criterion for metabolic syndrome, according to the International Diabetes Federation. As a proxy, the authors used a BMI of greater than 30 kg/m2. "While this might have affected the prevalence of metabolic syndrome in our study, we expect its impact on our analysis to be minor," they wrote.
Additionally, most celiac patients who started a gluten-free diet did not have endoscopic follow-up to assess intestinal healing.
However, "91.2% of these subjects had clinical improvement as well as normalization of their tTG titers, which increases the likelihood of histological improvement or remission."
None of the authors disclosed any financial conflicts relevant to this study. They disclosed no outside funding.
FROM GASTROENTEROLOGY
Major finding: The prevalence of type 2 diabetes among celiac disease patients was 3.1%, compared with 9.6% among control patients without celiac disease matched for age, sex, and ethnicity (P less than .0001).
Data source: A prevalence study of 840 patients with celiac disease and 840 matched controls.
Disclosures: None of the authors disclosed any financial conflicts relevant to this study. They disclosed no outside funding.
Concurrent NSAID, PPI use tapers over long term
Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.
Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).
Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.
Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.
Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.
A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.
Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.
According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).
By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).
The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).
"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.
According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."
Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).
The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.
"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.
The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
Factors increasing the risk for upper GI complications in NSAID users include older age (>60-75 years); prior upper GI complications or symptomatic ulcers; and concurrent use of aspirin, other antithrombotics, or corticosteroids. If patients cannot be switched to a non-NSAID analgesic, strategies recommended to decrease GI risk include PPI (or misoprostol) cotherapy or substitution of a COX-2 selective NSAID. Patients at very high risk (e.g., recent ulcer bleeding) should receive a COX-2 selective NSAID plus PPI (or misoprostol).
However, multiple observational studies demonstrate that most NSAID users with GI risk factors do not receive protective therapy. Importantly, adherence to a PPI more than 80% of the time is associated with significantly fewer upper GI clinical events than adherence less than 80% and less than 20% of the time.
The study by Le Ray et al looks at a group of NSAID users in whom a decision to provide a PPI prescription has been made. Co-therapy was stopped in 23% of patients at 1 year and 32% at 2 years. The authors correctly indicate that these patients likely are at increased risk. However, the rate of discontinuation was less than might have been anticipated (and less than in another European study), and half those discontinuing PPIs resumed them within 6 months. Furthermore, a number of patients had characteristics for which protective therapy is not generally recommended: e.g., heart disease, rheumatoid arthritis, dyspepsia, and celecoxib use.
Finally, the authors report that lack of PPI prescription was associated with increased GI “adverse events,” “injury,” and “complications.” We should note, however, that these “events” were primarily symptoms rather than complications or clinical events.
Loren Laine, M.D., AGAF, is a professor of medicine (digestive diseases) at Yale University, New Haven, Conn., and the Veterans Affairs Connecticut Healthcare System, West Haven. He also is the current president of the AGA Institute. He reported that he is a member of data safety monitoring boards on studies sponsored by Bayer, Eisai, Merck.
Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.
Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).
Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.
Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.
Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.
A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.
Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.
According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).
By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).
The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).
"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.
According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."
Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).
The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.
"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.
The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.
Among chronic nonsteroidal anti-inflammatory patients at high risk for a gastrointestinal bleeding, only two-thirds continue to be prescribed a proton pump inhibitor after 2 years.
Moreover, patients whose PPI prescriptions were discontinued were significantly more likely to experience a GI adverse event, compared with patients who had continuous NSAID and PPI coprescription, wrote Dr. Isabelle Le Ray and colleagues. The report was published in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.12.016).
Dr. Le Ray, of the Centre Hospitalier Universitaire de Dijon, France, and colleagues looked at records from the Longitudinal Patient Database, which collects data from a representative sample of 1,200 general practitioners in France.
Specifically, Dr. Le Ray focused on high-risk patients within the database who received a prescription for an NSAID for more than 7 days in 2007 plus a PPI, who renewed their NSAID within 6 months following the last prescription over a 2-year period.
Patients were considered to be high risk for a GI bleed if they were aged 65 years or older, had a history of upper GI disease, a co-prescription with an anticoagulant or antiplatelet medication, a previous bleed, and other comorbid conditions like rheumatoid arthritis.
A total of 1,856 patients met the criteria; most (74.4%) were over age 65, and 63.8% were female.
Although more than 14 different NSAIDs were prescribed, diclofenac, ketoprofen, piroxicam, and celecoxib accounted for the bulk of prescriptions. The median number of NSAID renewals during the 2-year period was 8, with a median of 30 days duration for each prescription.
According to the authors, at 12 months after initial NSAID/PPI prescription, the persistence probability of still having an active PPI prescription fell to 0.77(95% confidence interval, 0.75-0.79).
By 2 years, that likelihood fell to 0.68 (95% CI, 0.66-0.70).
The authors then looked at the presence of GI adverse events in this cohort. They found that 379 patients experienced an event, with patients who were not persistently prescribed a PPI at significantly higher risk, compared with patients whose PPI prescriptions never lapsed (odds ratio = 1.45; 95% CI, 1.06-2.09, P = .02).
"Absolute risk reduction associated with a continuous prescription of PPI with NSAIDs, in at-risk patients, was 3.2%," wrote the authors.
According to the researchers, factors associated with discontinuing a PPI included change from a given NSAID to a COX-2 inhibitor (multivariate hazard ratio for PPI discontinuation, 2.50; 95% CI, 1.91-3.28), despite the fact that "international guidelines recommend coprescription of a PPI for at-risk patients, even when using a COX-2 selective agent."
Being female also carried a high risk of stopping PPI treatment, (HR 1.25; 95%CI 1.05-1.49), while having multiple prescriptions for other drugs decreased the risk of PPI discontinuation (HR for stopping PPI 0.94 for each additional treatment; 95% CI, 0.91-0.96).
The study represents "the first time that the persistence of a prescription, i.e. systematic renewal of the [gastroprotective agent, the PPI] when the NSAID is being renewed, over time is characterized," the researchers said.
"These data suggest that the optimizing of [gastroprotective agent] coverage, mostly with a PPI, remains a major health issue among chronic NSAID users," they added.
The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major finding: By 24 months after initial NSAID/PPI coprescription, the persistence probability of still having an active PPI prescription fell to 0.68 (95% CI, 0.66-0.70).
Data source: A retrospective, observational, longitudinal study of 1,856 patients in France at risk for GI events.
Disclosures: The authors disclosed that this study was funded by the pharmaceutical company Ethypharm, for which one investigator is also an employee and another has served as a paid consultant. They added that this paper discusses no medications manufactured by Ethypharm.
Sofosbuvir shows sustained virologic response in HCV
Sofosbuvir resulted in a sustained virologic response in 90% of patients infected with hepatitis C virus genotype 1 or 4 at 12 weeks in a phase III trial.
Moreover, in a separate noninferiority analysis, patients with HCV genotypes 2 and 3 taking sofosbuvir had the same rates of sustained virologic response (SVR) as patients taking peginterferon, with fewer side effects, wrote Dr. Eric Lawitz in a report published online April 23 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1214853).
In a report that is also to be presented at the International Liver Congress in Amsterdam, Dr. Lawitz analyzed more than 1,000 previously untreated HCV patients who received treatment with sofosbuvir in two multicenter studies. Sofosbuvir is an investigational nucleotide analogue HCV NS5B polymerase inhibitor.
The first study, the NEUTRINO trial, looked at a single group of 327 patients with genotypes 1, 4, 5, and 6 who received 12 weeks of open-label treatment with sofosbuvir (400 mg/day) plus peginterferon alfa-2a (180 mcg once per week) and ribavirin (given as a divided dose according to body weight, at 1,000 mg/day for patients less than 75 kg and 1,200 mg/day for heavier patients).
Most (89%) of these patients were genotype 1, with 9% having genotype 4, and the remainder having types 5 or 6, according to Dr. Lawitz of the Texas Liver Institute at the University of Texas Health Science Center in San Antonio.
At 12 weeks, SVR, defined by the lower limit of quantification of 25 IU/mL, occurred in 295 of these 327 patients (90%), with little difference in response rate according to genotype.
Having cirrhosis reduced the regimen’s SVR rate to 80%.
The second study assessed by Dr. Lawitz, the FISSION trial, involved 499 patients with HCV genotypes 2 or 3, who were randomized to open-label treatment with either sofosbuvir plus ribavirin for 12 weeks (n = 256) or peginterferon alfa-2a plus ribavirin for 24 weeks (n = 243).
Dosages in the sofosbuvir group were the same as in the NEUTRINO trial; in the peginterferon group, the ribavirin was given as 800 mg/day in two divided doses.
In this analysis, the researchers found that at 12 weeks, both treatment groups had an SVR of 67%.
Once again, the presence of cirrhosis reduced the likelihood of SVR. Genotype 3 also lowered the response, giving SVR rates of 56% in the sofosbuvir group and 63% in the peginterferon group.
In both NEUTRINO and FISSION, deep sequencing analysis of patients taking sofosbuvir who relapsed after having a virologic response showed no evidence of resistance-associated variants.
Discontinuation of sofosbuvir because of adverse events was uncommon in both trials: 2% in the NEUTRINO and 1% in the FISSION.
Indeed, "the influenza-like symptoms and fever that are characteristic of interferon treatment were reported in 16% and 18% of patients receiving peginterferon, respectively, but in only 3% of patients receiving sofosbuvir," Dr. Lawitz and his colleagues wrote.
"Depression, another common side effect of interferon therapy, occurred in 14% of patients receiving peginterferon, as compared with 5% of patients receiving sofosbuvir."
Dr. Lawitz was an investigator in a second, unrelated study to be presented at the International Liver Congress and also reported in the New England Journal of Medicine. In that study, sofosbuvir was again proven to be effective in HCV genotype 2 and 3 patients for whom the traditional peginterferon-ribavirin regimen was not an option. Only the abstract of the study was available at press time (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMoa1214854]).
The NEUTRINO and FISSION trials were sponsored by Gilead Sciences, maker of sofosbuvir. Dr. Lawitz disclosed financial relationships to Gilead and multiple other pharmaceutical companies. Several authors were employees of Gilead.
The rapid change in the landscape for treating hepatitis C virus infection and the speed of drug development in the field – in the case of sofosbuvir, only a 3-year interval separates the publications of the chemical discovery of the protease inhibitor and its clinical data – may have negatively affected the design of clinical trials in the field.
For example, only one of the two studies conducted by Dr. Lawitz was a randomized controlled trial, and while the Food and Drug Administration has approved an endpoint of an SVR at 12 weeks (rather than the previously approved 24 weeks) for use in HCV trials, there is a small percentage (4%-6%) of patients with relapse of disease 12-24 weeks after treatment with sofosbuvir despite having an SVR. Although viral breakthrough does not appear to happen with sofosbuvir and did not occur in any of these patients, they somehow still relapsed despite meeting the trial’s definition for SVR; the reasons for relapse remain unknown.
However, these concerns may be outweighed by the sofosbuvir regimen’s low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drug .
Dr. Joost P.H. Drenth is in the department of gastroenterology and hepatology at Radboud University Nijmegen (the Netherlands) Medical Center. He disclosed previous grants from Gilead Sciences, maker of sofosbuvir, and other pharmaceutical companies. His comments are derived from his editorial accompanying the sofosbuvir studies (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMe1303818]).
The rapid change in the landscape for treating hepatitis C virus infection and the speed of drug development in the field – in the case of sofosbuvir, only a 3-year interval separates the publications of the chemical discovery of the protease inhibitor and its clinical data – may have negatively affected the design of clinical trials in the field.
For example, only one of the two studies conducted by Dr. Lawitz was a randomized controlled trial, and while the Food and Drug Administration has approved an endpoint of an SVR at 12 weeks (rather than the previously approved 24 weeks) for use in HCV trials, there is a small percentage (4%-6%) of patients with relapse of disease 12-24 weeks after treatment with sofosbuvir despite having an SVR. Although viral breakthrough does not appear to happen with sofosbuvir and did not occur in any of these patients, they somehow still relapsed despite meeting the trial’s definition for SVR; the reasons for relapse remain unknown.
However, these concerns may be outweighed by the sofosbuvir regimen’s low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drug .
Dr. Joost P.H. Drenth is in the department of gastroenterology and hepatology at Radboud University Nijmegen (the Netherlands) Medical Center. He disclosed previous grants from Gilead Sciences, maker of sofosbuvir, and other pharmaceutical companies. His comments are derived from his editorial accompanying the sofosbuvir studies (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMe1303818]).
The rapid change in the landscape for treating hepatitis C virus infection and the speed of drug development in the field – in the case of sofosbuvir, only a 3-year interval separates the publications of the chemical discovery of the protease inhibitor and its clinical data – may have negatively affected the design of clinical trials in the field.
For example, only one of the two studies conducted by Dr. Lawitz was a randomized controlled trial, and while the Food and Drug Administration has approved an endpoint of an SVR at 12 weeks (rather than the previously approved 24 weeks) for use in HCV trials, there is a small percentage (4%-6%) of patients with relapse of disease 12-24 weeks after treatment with sofosbuvir despite having an SVR. Although viral breakthrough does not appear to happen with sofosbuvir and did not occur in any of these patients, they somehow still relapsed despite meeting the trial’s definition for SVR; the reasons for relapse remain unknown.
However, these concerns may be outweighed by the sofosbuvir regimen’s low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drug .
Dr. Joost P.H. Drenth is in the department of gastroenterology and hepatology at Radboud University Nijmegen (the Netherlands) Medical Center. He disclosed previous grants from Gilead Sciences, maker of sofosbuvir, and other pharmaceutical companies. His comments are derived from his editorial accompanying the sofosbuvir studies (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMe1303818]).
Sofosbuvir resulted in a sustained virologic response in 90% of patients infected with hepatitis C virus genotype 1 or 4 at 12 weeks in a phase III trial.
Moreover, in a separate noninferiority analysis, patients with HCV genotypes 2 and 3 taking sofosbuvir had the same rates of sustained virologic response (SVR) as patients taking peginterferon, with fewer side effects, wrote Dr. Eric Lawitz in a report published online April 23 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1214853).
In a report that is also to be presented at the International Liver Congress in Amsterdam, Dr. Lawitz analyzed more than 1,000 previously untreated HCV patients who received treatment with sofosbuvir in two multicenter studies. Sofosbuvir is an investigational nucleotide analogue HCV NS5B polymerase inhibitor.
The first study, the NEUTRINO trial, looked at a single group of 327 patients with genotypes 1, 4, 5, and 6 who received 12 weeks of open-label treatment with sofosbuvir (400 mg/day) plus peginterferon alfa-2a (180 mcg once per week) and ribavirin (given as a divided dose according to body weight, at 1,000 mg/day for patients less than 75 kg and 1,200 mg/day for heavier patients).
Most (89%) of these patients were genotype 1, with 9% having genotype 4, and the remainder having types 5 or 6, according to Dr. Lawitz of the Texas Liver Institute at the University of Texas Health Science Center in San Antonio.
At 12 weeks, SVR, defined by the lower limit of quantification of 25 IU/mL, occurred in 295 of these 327 patients (90%), with little difference in response rate according to genotype.
Having cirrhosis reduced the regimen’s SVR rate to 80%.
The second study assessed by Dr. Lawitz, the FISSION trial, involved 499 patients with HCV genotypes 2 or 3, who were randomized to open-label treatment with either sofosbuvir plus ribavirin for 12 weeks (n = 256) or peginterferon alfa-2a plus ribavirin for 24 weeks (n = 243).
Dosages in the sofosbuvir group were the same as in the NEUTRINO trial; in the peginterferon group, the ribavirin was given as 800 mg/day in two divided doses.
In this analysis, the researchers found that at 12 weeks, both treatment groups had an SVR of 67%.
Once again, the presence of cirrhosis reduced the likelihood of SVR. Genotype 3 also lowered the response, giving SVR rates of 56% in the sofosbuvir group and 63% in the peginterferon group.
In both NEUTRINO and FISSION, deep sequencing analysis of patients taking sofosbuvir who relapsed after having a virologic response showed no evidence of resistance-associated variants.
Discontinuation of sofosbuvir because of adverse events was uncommon in both trials: 2% in the NEUTRINO and 1% in the FISSION.
Indeed, "the influenza-like symptoms and fever that are characteristic of interferon treatment were reported in 16% and 18% of patients receiving peginterferon, respectively, but in only 3% of patients receiving sofosbuvir," Dr. Lawitz and his colleagues wrote.
"Depression, another common side effect of interferon therapy, occurred in 14% of patients receiving peginterferon, as compared with 5% of patients receiving sofosbuvir."
Dr. Lawitz was an investigator in a second, unrelated study to be presented at the International Liver Congress and also reported in the New England Journal of Medicine. In that study, sofosbuvir was again proven to be effective in HCV genotype 2 and 3 patients for whom the traditional peginterferon-ribavirin regimen was not an option. Only the abstract of the study was available at press time (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMoa1214854]).
The NEUTRINO and FISSION trials were sponsored by Gilead Sciences, maker of sofosbuvir. Dr. Lawitz disclosed financial relationships to Gilead and multiple other pharmaceutical companies. Several authors were employees of Gilead.
Sofosbuvir resulted in a sustained virologic response in 90% of patients infected with hepatitis C virus genotype 1 or 4 at 12 weeks in a phase III trial.
Moreover, in a separate noninferiority analysis, patients with HCV genotypes 2 and 3 taking sofosbuvir had the same rates of sustained virologic response (SVR) as patients taking peginterferon, with fewer side effects, wrote Dr. Eric Lawitz in a report published online April 23 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1214853).
In a report that is also to be presented at the International Liver Congress in Amsterdam, Dr. Lawitz analyzed more than 1,000 previously untreated HCV patients who received treatment with sofosbuvir in two multicenter studies. Sofosbuvir is an investigational nucleotide analogue HCV NS5B polymerase inhibitor.
The first study, the NEUTRINO trial, looked at a single group of 327 patients with genotypes 1, 4, 5, and 6 who received 12 weeks of open-label treatment with sofosbuvir (400 mg/day) plus peginterferon alfa-2a (180 mcg once per week) and ribavirin (given as a divided dose according to body weight, at 1,000 mg/day for patients less than 75 kg and 1,200 mg/day for heavier patients).
Most (89%) of these patients were genotype 1, with 9% having genotype 4, and the remainder having types 5 or 6, according to Dr. Lawitz of the Texas Liver Institute at the University of Texas Health Science Center in San Antonio.
At 12 weeks, SVR, defined by the lower limit of quantification of 25 IU/mL, occurred in 295 of these 327 patients (90%), with little difference in response rate according to genotype.
Having cirrhosis reduced the regimen’s SVR rate to 80%.
The second study assessed by Dr. Lawitz, the FISSION trial, involved 499 patients with HCV genotypes 2 or 3, who were randomized to open-label treatment with either sofosbuvir plus ribavirin for 12 weeks (n = 256) or peginterferon alfa-2a plus ribavirin for 24 weeks (n = 243).
Dosages in the sofosbuvir group were the same as in the NEUTRINO trial; in the peginterferon group, the ribavirin was given as 800 mg/day in two divided doses.
In this analysis, the researchers found that at 12 weeks, both treatment groups had an SVR of 67%.
Once again, the presence of cirrhosis reduced the likelihood of SVR. Genotype 3 also lowered the response, giving SVR rates of 56% in the sofosbuvir group and 63% in the peginterferon group.
In both NEUTRINO and FISSION, deep sequencing analysis of patients taking sofosbuvir who relapsed after having a virologic response showed no evidence of resistance-associated variants.
Discontinuation of sofosbuvir because of adverse events was uncommon in both trials: 2% in the NEUTRINO and 1% in the FISSION.
Indeed, "the influenza-like symptoms and fever that are characteristic of interferon treatment were reported in 16% and 18% of patients receiving peginterferon, respectively, but in only 3% of patients receiving sofosbuvir," Dr. Lawitz and his colleagues wrote.
"Depression, another common side effect of interferon therapy, occurred in 14% of patients receiving peginterferon, as compared with 5% of patients receiving sofosbuvir."
Dr. Lawitz was an investigator in a second, unrelated study to be presented at the International Liver Congress and also reported in the New England Journal of Medicine. In that study, sofosbuvir was again proven to be effective in HCV genotype 2 and 3 patients for whom the traditional peginterferon-ribavirin regimen was not an option. Only the abstract of the study was available at press time (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMoa1214854]).
The NEUTRINO and FISSION trials were sponsored by Gilead Sciences, maker of sofosbuvir. Dr. Lawitz disclosed financial relationships to Gilead and multiple other pharmaceutical companies. Several authors were employees of Gilead.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major finding: A regimen containing sofosbuvir gave 90% of patients with genotype 1 or 4 HCV infection an SVR at 12 weeks, whereas genotype 2 and 3 patients had a 12-week SVR rate of 67%.
Data source: Two phase III studies (one single-group, open-label study and one randomized, open-label, active-control trial) of more than 1,000 patients
Disclosures: The NEUTRINO and FISSION trials were sponsored by Gilead Sciences, maker of sofosbuvir. Dr. Lawitz disclosed financial relationships to Gilead and multiple other pharmaceutical companies. Several authors were employees of Gilead.
Twelve-step programs beneficial in comorbid substance use, psychotic disorders
Patients with comorbid substance use and psychotic disorders do indeed benefit from standard substance use treatment that is not integrated with their psychiatric diagnosis, including both 12-step and cognitive-behavioral programs.
The finding validates the standard, nonintegrated treatment that is currently most prevalent among this cohort, especially veterans, according to an analysis in Schizophrenia Research.
The study, by Matthew Tyler Boden, Ph.D., and Rudolf Moos, Ph.D., both of the Center for Health Care Evaluation at Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 236 male patients with comorbid substance use and non-substance–related psychotic disorders.
All patients sought treatment at one of 15 residential substance use disorder programs affiliated with the Department of Veterans Affairs (Schizophr. Res. 2013;146:28-33).
The mean age was 41 years; 50% were white, 44.5% were black, and the average reported education level among the cohort was 13 years.
Most of the patients (62.7%) had schizophrenia; the remainder had a psychotic disorder related to affect, such as schizoaffective disorder.
According to the authors, patients in cognitive-behavioral programs participated in small therapy and relapse prevention groups. They also attended cognitive, behavioral, and abstinence skills training groups.
The 12-step programs, on the other hand, encouraged patients to see themselves as addicts or alcoholics, and to acknowledge that they were powerless or had little control over abused substances. These self-help programs also encouraged the patients to adhere to the treatment goal of abstinence, wrote the authors.
Both groups experienced similar results in the near term, in what the investigators called "proximal" outcomes: In both groups, active coping significantly increased and avoidant coping significantly decreased from initiation to discharge.
Indeed, it wasn’t the type of program, but the degree of patient satisfaction that predicted results.
"Patients who perceived the treatment milieu more positively (greater support, spontaneity, spirituality, personal problem orientation) and reported more satisfaction tended to show better proximal outcomes, especially in terms of self-efficacy and approach coping," the researchers noted.
In turn, "patients who had better proximal outcomes at discharge (especially more self-efficacy and less reliance on avoidance coping) tended to show fewer psychiatric symptoms and less substance use at 1 year," they wrote.
The investigators noted that patients who participated in the 12-step programs experienced better 5-year substance use outcomes.
The study could not assess the mechanisms that led to improvement, nor could it accurately compare the two different program modalities, the researchers said. Additionally, the study was hampered by the lack of a control group, which "limits our ability to determine whether changes were due to treatment or to natural improvement over time."
Finally, they wrote that their population of male veterans might also limit the study’s generalizability to other cohorts, such as women and nonveteran patients with comorbid substance use and psychotic disorders.
"Although experts are consistent in their recommendations for treating [substance use disorder/psychotic disorder] patients with an integrated approach, and integrated approaches are effective, our results suggest that [these] patients may benefit from standard [substance use disorder] treatments, even those that may not directly address their psychiatric disorders," the authors wrote.
"These findings suggest that [substance use disorder] treatment programs could benefit [substance use disorder/psychotic disorder] patients by allocating more resources to enhance positive reactions to treatment and improve proximal outcomes, such as self-efficacy and avoidant coping," they added.
The study was supported by the Veterans Health Administration. The authors declared having no conflicts of interest.
Patients with comorbid substance use and psychotic disorders do indeed benefit from standard substance use treatment that is not integrated with their psychiatric diagnosis, including both 12-step and cognitive-behavioral programs.
The finding validates the standard, nonintegrated treatment that is currently most prevalent among this cohort, especially veterans, according to an analysis in Schizophrenia Research.
The study, by Matthew Tyler Boden, Ph.D., and Rudolf Moos, Ph.D., both of the Center for Health Care Evaluation at Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 236 male patients with comorbid substance use and non-substance–related psychotic disorders.
All patients sought treatment at one of 15 residential substance use disorder programs affiliated with the Department of Veterans Affairs (Schizophr. Res. 2013;146:28-33).
The mean age was 41 years; 50% were white, 44.5% were black, and the average reported education level among the cohort was 13 years.
Most of the patients (62.7%) had schizophrenia; the remainder had a psychotic disorder related to affect, such as schizoaffective disorder.
According to the authors, patients in cognitive-behavioral programs participated in small therapy and relapse prevention groups. They also attended cognitive, behavioral, and abstinence skills training groups.
The 12-step programs, on the other hand, encouraged patients to see themselves as addicts or alcoholics, and to acknowledge that they were powerless or had little control over abused substances. These self-help programs also encouraged the patients to adhere to the treatment goal of abstinence, wrote the authors.
Both groups experienced similar results in the near term, in what the investigators called "proximal" outcomes: In both groups, active coping significantly increased and avoidant coping significantly decreased from initiation to discharge.
Indeed, it wasn’t the type of program, but the degree of patient satisfaction that predicted results.
"Patients who perceived the treatment milieu more positively (greater support, spontaneity, spirituality, personal problem orientation) and reported more satisfaction tended to show better proximal outcomes, especially in terms of self-efficacy and approach coping," the researchers noted.
In turn, "patients who had better proximal outcomes at discharge (especially more self-efficacy and less reliance on avoidance coping) tended to show fewer psychiatric symptoms and less substance use at 1 year," they wrote.
The investigators noted that patients who participated in the 12-step programs experienced better 5-year substance use outcomes.
The study could not assess the mechanisms that led to improvement, nor could it accurately compare the two different program modalities, the researchers said. Additionally, the study was hampered by the lack of a control group, which "limits our ability to determine whether changes were due to treatment or to natural improvement over time."
Finally, they wrote that their population of male veterans might also limit the study’s generalizability to other cohorts, such as women and nonveteran patients with comorbid substance use and psychotic disorders.
"Although experts are consistent in their recommendations for treating [substance use disorder/psychotic disorder] patients with an integrated approach, and integrated approaches are effective, our results suggest that [these] patients may benefit from standard [substance use disorder] treatments, even those that may not directly address their psychiatric disorders," the authors wrote.
"These findings suggest that [substance use disorder] treatment programs could benefit [substance use disorder/psychotic disorder] patients by allocating more resources to enhance positive reactions to treatment and improve proximal outcomes, such as self-efficacy and avoidant coping," they added.
The study was supported by the Veterans Health Administration. The authors declared having no conflicts of interest.
Patients with comorbid substance use and psychotic disorders do indeed benefit from standard substance use treatment that is not integrated with their psychiatric diagnosis, including both 12-step and cognitive-behavioral programs.
The finding validates the standard, nonintegrated treatment that is currently most prevalent among this cohort, especially veterans, according to an analysis in Schizophrenia Research.
The study, by Matthew Tyler Boden, Ph.D., and Rudolf Moos, Ph.D., both of the Center for Health Care Evaluation at Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 236 male patients with comorbid substance use and non-substance–related psychotic disorders.
All patients sought treatment at one of 15 residential substance use disorder programs affiliated with the Department of Veterans Affairs (Schizophr. Res. 2013;146:28-33).
The mean age was 41 years; 50% were white, 44.5% were black, and the average reported education level among the cohort was 13 years.
Most of the patients (62.7%) had schizophrenia; the remainder had a psychotic disorder related to affect, such as schizoaffective disorder.
According to the authors, patients in cognitive-behavioral programs participated in small therapy and relapse prevention groups. They also attended cognitive, behavioral, and abstinence skills training groups.
The 12-step programs, on the other hand, encouraged patients to see themselves as addicts or alcoholics, and to acknowledge that they were powerless or had little control over abused substances. These self-help programs also encouraged the patients to adhere to the treatment goal of abstinence, wrote the authors.
Both groups experienced similar results in the near term, in what the investigators called "proximal" outcomes: In both groups, active coping significantly increased and avoidant coping significantly decreased from initiation to discharge.
Indeed, it wasn’t the type of program, but the degree of patient satisfaction that predicted results.
"Patients who perceived the treatment milieu more positively (greater support, spontaneity, spirituality, personal problem orientation) and reported more satisfaction tended to show better proximal outcomes, especially in terms of self-efficacy and approach coping," the researchers noted.
In turn, "patients who had better proximal outcomes at discharge (especially more self-efficacy and less reliance on avoidance coping) tended to show fewer psychiatric symptoms and less substance use at 1 year," they wrote.
The investigators noted that patients who participated in the 12-step programs experienced better 5-year substance use outcomes.
The study could not assess the mechanisms that led to improvement, nor could it accurately compare the two different program modalities, the researchers said. Additionally, the study was hampered by the lack of a control group, which "limits our ability to determine whether changes were due to treatment or to natural improvement over time."
Finally, they wrote that their population of male veterans might also limit the study’s generalizability to other cohorts, such as women and nonveteran patients with comorbid substance use and psychotic disorders.
"Although experts are consistent in their recommendations for treating [substance use disorder/psychotic disorder] patients with an integrated approach, and integrated approaches are effective, our results suggest that [these] patients may benefit from standard [substance use disorder] treatments, even those that may not directly address their psychiatric disorders," the authors wrote.
"These findings suggest that [substance use disorder] treatment programs could benefit [substance use disorder/psychotic disorder] patients by allocating more resources to enhance positive reactions to treatment and improve proximal outcomes, such as self-efficacy and avoidant coping," they added.
The study was supported by the Veterans Health Administration. The authors declared having no conflicts of interest.
FROM SCHIZOPHRENIA RESEARCH
Major finding: Patients with comorbid substance use and psychotic disorders can benefit from standard substance use treatments, even though they do not directly address patients’ psychotic diagnoses.
Data source: A longitudinal cohort of 236 male veterans with comorbid substance use disorder and psychotic disorder undergoing standard substance use disorder treatment.
Disclosures: The authors disclosed that the study was supported by the Veterans Health Administration. They declared having no individual conflicts of interest.
Manometric type II achalasia patients have best outcomes
In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.
Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).
Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).
In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.
In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.
Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).
Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.
In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.
The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.
"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).
Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).
In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.
The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.
They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."
Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.
The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.
 |
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
|
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
|
| Dr. John Pandolfino |
Additionally, this paper also suggests that the achalasia subtypes developed using EPT can be assessed with conventional manometry, supporting the notion that this classification scheme is independent of the technology used. Achalasia subtypes have long been recognized with conventional manometry, however, the categories were somewhat vague and poorly described. Vigorous achalasia was a terminology utilized to describe atypical disorders of LES relaxation using the presence of some preserved peristalsis or simultaneous contractions to distinguish this pattern from classic achalasia (type I achalasia). Leveraging the detail from EPT, patients lumped into the “vigorous” category can now be separated into three distinct subtypes: type II (associated with panesophageal pressurization), type III (associated with spastic contractions) and esophagogastric junction (EGJ) outflow obstruction (associated with preserved peristalsis).
These subtypes are very different in terms of the prognosis and management. Type II patients have an excellent prognosis and while type III has a much poorer outcome due to the overlapping spastic features, which are difficult to treat. EGJ outflow obstruction is a unique diagnosis that can present as achalasia, but may also be associated with a subtle mechanical obstruction. Thus, defining these subtypes will alter management of patients with achalasia and these subtypes should not be overlooked in future research studies focused on achalasia pathogenesis and treatment.
John Pandolfino, M.D., AGAF, is a professor of medicine at the Feinberg School of Medicine at Northwestern University, Chicago. He is a consultant for Given Imaging, Sandhill Scientific, and Medical Measurement Systems. He is also a speaker for AstraZeneca and Given Imaging.
In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.
Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).
Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).
In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.
In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.
Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).
Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.
In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.
The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.
"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).
Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).
In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.
The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.
They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."
Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.
The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.
In achalasia, manometric subtype II patients have the greatest treatment success rates, compared with type I and type III patients.
Moreover, the finding applies both to patients treated with pneumatic dilation and to those treated with laparoscopic Heller myotomy, which have comparable high success rates in this population, reported Dr. Wout O. Rohof and Dr. Renato Salvador in the April issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.027).
Lead coauthors Dr. Rohof and Dr. Salvador, from the Academic Medical Center in Amsterdam and the Padova (Italy) University Hospital, respectively, and their colleagues looked at data from nearly 200 patients who participated in the previously published European Achalasia Trial (N. Engl. J. Med. 2011;364:1807-16).
In that study, 201 patients were randomly assigned to undergo either pneumatic dilation or Heller myotomy, with the result being that both treatments produced equally high success rates in achalasia patients.
In the current study, the investigators looked at the 176 patients for whom pretreatment conventional myometric grading was available, to see whether treatment response rates were higher in subtype I, II, or III.
Briefly, according to Pandolfino et al., subtype I refers to patients in whom the esophageal body exhibits minimal contractility; type II to patients who lack peristalsis but demonstrate intermittent periods of compartmentalized esophageal pressurization; and type III to patients who exhibit spastic contractions in the distal esophagus (Gastroenterology 2008;135:1526-33).
Overall, 44 patients (25%) had achalasia type I, 114 (65%) had type II, and 18 (10%) type III.
In the European Achalasia Trial, there were no statistically significant differences in age or sex between patient subtypes, and subtypes were equally distributed over the two treatment protocols, wrote the authors.
The researchers found that among type I patients, there was no significant difference in success rates between dilation and myotomy (81% vs. 85%, respectively; P less than .01), with success defined as a drop in Eckardt score to 3 or less at 1 year post treatment.
"In contrast, in type II, the success rate for dilation was significantly higher than that of myotomy, ... with 100% treatment success in the [dilation] group, compared to 93% in the [myotomy] group," the authors wrote (P less than .05).
Type III patients, in contrast, had overall lower success rates, with 86% for myotomy and 40% for dilation (the difference between the groups could not be assessed for significance because there were too few patients with type III achalasia).
In any case, "irrespective of treatment arm, success rate after a mean follow-up of 43 months was significantly higher in patients with type II compared to type I (P less than .01) and type III (P less than .001)," the researchers wrote.
The authors conceded that the manometry subtype classification system developed by Pandolfino was designed for use with high-resolution manometry instead of the conventional manometry used in their study.
They noted, however, that at least one study has found 100% agreement between the classification of subtypes based on conventional pressure line tracings versus high-resolution manometry plots, and "our three patient groups were similar to those reported by Pandolfino, in terms of both clinical features and outcome after therapy."
Indeed, "based on our findings, we conclude that when a graded distension protocol allowing redilation is used, pneumatic dilation and laparoscopic Heller myotomy are both appropriate treatment options for type I and type II achalasia, at least until longer follow-up data are available," the authors concluded.
The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.
FROM GASTROENTEROLOGY
Major finding: Patients with manometric type II achalasia have higher success rates after dilation (93%) as well as myotomy (100%) at 1 year, compared with patients who have subtypes I and III.
Data source: A total of 176 patients enrolled in the prospective, randomized, multicenter European Achalasia Trial.
Disclosures: The researchers stated that they had no competing interests to disclose in relation to this study. One of the authors disclosed being funded by a grant from the Flemish government.
MR colonography has utility in high-risk lesions
Magnetic resonance colonography identified asymptomatic adults with adenomas of 6 mm or larger and advanced adenomas with sensitivities of 78.4% and 75%, respectively.
"If primary screening by colonoscopy is not performed, MR colonography appears to be a better option than a one-time fecal occult blood test" for detecting high-risk lesions, without the radiation associated with computed tomography, reported Dr. Anno Graser and his colleagues in the April 1 issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.041).
Dr. Graser of the University of Munich and his colleagues looked at 286 asymptomatic adults aged 50 years or older with an average risk of colorectal cancer and asymptomatic adults aged 40 years or older with a family history of colorectal cancer (175 men; mean age, 59 years).
Patients were excluded if they had any prior colonoscopy, symptoms or history of bowel disease, significant weight loss, body weight greater than 150 kg, relevant cardiovascular or pulmonary comorbidity, or contraindications to MR scanning.
All patients underwent fecal occult blood testing prior to bowel preparation, and then underwent both colonoscopy and MR colonography on the same day.
Overall, colonoscopy detected 281 luminal lesions, including one adenocarcinoma of the rectum, one squamous cell carcinoma of the anal canal, and 133 adenomas in 85 patients, including 20 advanced adenomas in 17 patients. There were also 129 hyperplastic polyps detected on colonoscopy, as well as 17 other benign lesions.
MR colonography, on the other hand, detected the two cancers, as well as 43 (32.3%) adenomas, including 29 (78.4%) adenomas of 6 mm or greater.
MR colonography also detected 15 (75%) advanced adenomas and 11 (8.5%) hyperplastic polyps.
"There were no complications in either the MR colonographies or the colonoscopies," wrote the authors.
In contrast, fecal occult blood testing found just 3 of 30 patients (10%) with adenomas of 6 mm or greater and 3 of 17 patients (17.6%) with advanced neoplasia.
MR colonography also identified several "potentially important extracolonic findings" in eight (2.8%) patients: three patients with renal masses; two with bulky retroperitoneal lymphadenopathy "representing manifestations of a newly diagnosed diffuse large-cell lymphoma and a chronic lymphatic leukemia, respectively"; one with a serous cystadenoma of the pancreas; and two with aortic aneurysms greater than 5 cm, the authors reported.
In terms of specificity, for adenomas 6 mm or larger, the specificity was 96.9% for colonoscopy, 95.3% for MR colonography, and 91.8% for fecal occult blood testing.
Similarly, for advanced neoplasia the figures were 48.5%, 81.0%, and 92.2% for colonoscopy, MR colonography, and fecal occult blood testing, respectively.
The authors also compared MR colonography in their study to previous studies of CT colonography, which has been shown to have a sensitivity for advanced neoplasia of 96% (Gut 2009;58:241-8).
"Still, the major advantage of MR colonography over CT colonography is that it does not apply ionizing radiation," wrote the authors.
There are several limitations to the technique, the authors said. For one, MR colonography requires gadolinium-based intravenous contrast. However, except for patients with impaired renal function, this is usually well tolerated.
MR colonography has a limited sensitivity for lesions of 5 mm or less, because of the technique’s limited spatial resolution and lack of significant enhancement of diminutive polyps.
However, "as these lesions only carry a low risk of malignancy, this limitation of MR colonography may not impair its potential use as a screening tool."
Finally, "in the light of cost-effectiveness discussions, MR colonography as a relatively expensive test has to be weighed carefully against the cost of colonoscopy," wrote the researchers.
The authors declared that they had no relevant financial conflicts and that the study had no outside funding.
Magnetic resonance colonography identified asymptomatic adults with adenomas of 6 mm or larger and advanced adenomas with sensitivities of 78.4% and 75%, respectively.
"If primary screening by colonoscopy is not performed, MR colonography appears to be a better option than a one-time fecal occult blood test" for detecting high-risk lesions, without the radiation associated with computed tomography, reported Dr. Anno Graser and his colleagues in the April 1 issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.041).
Dr. Graser of the University of Munich and his colleagues looked at 286 asymptomatic adults aged 50 years or older with an average risk of colorectal cancer and asymptomatic adults aged 40 years or older with a family history of colorectal cancer (175 men; mean age, 59 years).
Patients were excluded if they had any prior colonoscopy, symptoms or history of bowel disease, significant weight loss, body weight greater than 150 kg, relevant cardiovascular or pulmonary comorbidity, or contraindications to MR scanning.
All patients underwent fecal occult blood testing prior to bowel preparation, and then underwent both colonoscopy and MR colonography on the same day.
Overall, colonoscopy detected 281 luminal lesions, including one adenocarcinoma of the rectum, one squamous cell carcinoma of the anal canal, and 133 adenomas in 85 patients, including 20 advanced adenomas in 17 patients. There were also 129 hyperplastic polyps detected on colonoscopy, as well as 17 other benign lesions.
MR colonography, on the other hand, detected the two cancers, as well as 43 (32.3%) adenomas, including 29 (78.4%) adenomas of 6 mm or greater.
MR colonography also detected 15 (75%) advanced adenomas and 11 (8.5%) hyperplastic polyps.
"There were no complications in either the MR colonographies or the colonoscopies," wrote the authors.
In contrast, fecal occult blood testing found just 3 of 30 patients (10%) with adenomas of 6 mm or greater and 3 of 17 patients (17.6%) with advanced neoplasia.
MR colonography also identified several "potentially important extracolonic findings" in eight (2.8%) patients: three patients with renal masses; two with bulky retroperitoneal lymphadenopathy "representing manifestations of a newly diagnosed diffuse large-cell lymphoma and a chronic lymphatic leukemia, respectively"; one with a serous cystadenoma of the pancreas; and two with aortic aneurysms greater than 5 cm, the authors reported.
In terms of specificity, for adenomas 6 mm or larger, the specificity was 96.9% for colonoscopy, 95.3% for MR colonography, and 91.8% for fecal occult blood testing.
Similarly, for advanced neoplasia the figures were 48.5%, 81.0%, and 92.2% for colonoscopy, MR colonography, and fecal occult blood testing, respectively.
The authors also compared MR colonography in their study to previous studies of CT colonography, which has been shown to have a sensitivity for advanced neoplasia of 96% (Gut 2009;58:241-8).
"Still, the major advantage of MR colonography over CT colonography is that it does not apply ionizing radiation," wrote the authors.
There are several limitations to the technique, the authors said. For one, MR colonography requires gadolinium-based intravenous contrast. However, except for patients with impaired renal function, this is usually well tolerated.
MR colonography has a limited sensitivity for lesions of 5 mm or less, because of the technique’s limited spatial resolution and lack of significant enhancement of diminutive polyps.
However, "as these lesions only carry a low risk of malignancy, this limitation of MR colonography may not impair its potential use as a screening tool."
Finally, "in the light of cost-effectiveness discussions, MR colonography as a relatively expensive test has to be weighed carefully against the cost of colonoscopy," wrote the researchers.
The authors declared that they had no relevant financial conflicts and that the study had no outside funding.
Magnetic resonance colonography identified asymptomatic adults with adenomas of 6 mm or larger and advanced adenomas with sensitivities of 78.4% and 75%, respectively.
"If primary screening by colonoscopy is not performed, MR colonography appears to be a better option than a one-time fecal occult blood test" for detecting high-risk lesions, without the radiation associated with computed tomography, reported Dr. Anno Graser and his colleagues in the April 1 issue of Gastroenterology (doi: 10.1053/j.gastro.2012.12.041).
Dr. Graser of the University of Munich and his colleagues looked at 286 asymptomatic adults aged 50 years or older with an average risk of colorectal cancer and asymptomatic adults aged 40 years or older with a family history of colorectal cancer (175 men; mean age, 59 years).
Patients were excluded if they had any prior colonoscopy, symptoms or history of bowel disease, significant weight loss, body weight greater than 150 kg, relevant cardiovascular or pulmonary comorbidity, or contraindications to MR scanning.
All patients underwent fecal occult blood testing prior to bowel preparation, and then underwent both colonoscopy and MR colonography on the same day.
Overall, colonoscopy detected 281 luminal lesions, including one adenocarcinoma of the rectum, one squamous cell carcinoma of the anal canal, and 133 adenomas in 85 patients, including 20 advanced adenomas in 17 patients. There were also 129 hyperplastic polyps detected on colonoscopy, as well as 17 other benign lesions.
MR colonography, on the other hand, detected the two cancers, as well as 43 (32.3%) adenomas, including 29 (78.4%) adenomas of 6 mm or greater.
MR colonography also detected 15 (75%) advanced adenomas and 11 (8.5%) hyperplastic polyps.
"There were no complications in either the MR colonographies or the colonoscopies," wrote the authors.
In contrast, fecal occult blood testing found just 3 of 30 patients (10%) with adenomas of 6 mm or greater and 3 of 17 patients (17.6%) with advanced neoplasia.
MR colonography also identified several "potentially important extracolonic findings" in eight (2.8%) patients: three patients with renal masses; two with bulky retroperitoneal lymphadenopathy "representing manifestations of a newly diagnosed diffuse large-cell lymphoma and a chronic lymphatic leukemia, respectively"; one with a serous cystadenoma of the pancreas; and two with aortic aneurysms greater than 5 cm, the authors reported.
In terms of specificity, for adenomas 6 mm or larger, the specificity was 96.9% for colonoscopy, 95.3% for MR colonography, and 91.8% for fecal occult blood testing.
Similarly, for advanced neoplasia the figures were 48.5%, 81.0%, and 92.2% for colonoscopy, MR colonography, and fecal occult blood testing, respectively.
The authors also compared MR colonography in their study to previous studies of CT colonography, which has been shown to have a sensitivity for advanced neoplasia of 96% (Gut 2009;58:241-8).
"Still, the major advantage of MR colonography over CT colonography is that it does not apply ionizing radiation," wrote the authors.
There are several limitations to the technique, the authors said. For one, MR colonography requires gadolinium-based intravenous contrast. However, except for patients with impaired renal function, this is usually well tolerated.
MR colonography has a limited sensitivity for lesions of 5 mm or less, because of the technique’s limited spatial resolution and lack of significant enhancement of diminutive polyps.
However, "as these lesions only carry a low risk of malignancy, this limitation of MR colonography may not impair its potential use as a screening tool."
Finally, "in the light of cost-effectiveness discussions, MR colonography as a relatively expensive test has to be weighed carefully against the cost of colonoscopy," wrote the researchers.
The authors declared that they had no relevant financial conflicts and that the study had no outside funding.
FROM GASTROENTEROLOGY
Major finding: Magnetic resonance colonography had a sensitivity of 78.4% for detecting adenomas greater than or equal to 6 mm.
Data source: A blinded study of 286 asymptomatic adults undergoing magnetic resonance colonography and colonoscopy on the same day.
Disclosures: The authors declared that they had no relevant financial conflicts and that the study had no outside funding.