User login
About 13% of liver transplant recipients affected by PTSD
SAN FRANCISCO –
“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.
Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.
The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.
The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).
On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.
One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”
In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.
The researchers reported having no financial disclosures.
SAN FRANCISCO –
“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.
Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.
The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.
The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).
On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.
One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”
In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.
The researchers reported having no financial disclosures.
SAN FRANCISCO –
“Serving the emotional and mental health of these patients is just as important as [improving] liver function and their immunosuppression,” study author Meg O’Meara, NP, said in an interview at the annual meeting of the American Association for the Study of Liver Diseases.
Recent data suggests that patients who undergo significant medical events like solid organ transplantation face a risk of developing PTSD, but limited information exists regarding the psychological effects following adult liver transplantation, said Ms. O’Meara, a nurse practitioner in the division of gastroenterology and hepatology at the University of Colorado at Denver, Aurora. In an effort to determine the prevalence of and risk factors for PTSD in adult liver transplant recipients, she and her associates used the PCL-5 to screen 71 patients seen at the university’s posttransplant clinic from Dec. 1, 2017, to May 31, 2018. The PCL-5 is a validated 20-item questionnaire that corresponds to the DSM-5 symptom criteria for PTSD.
The researchers also collected clinical and demographic information including pretransplant disease severity, history of psychiatric disease, duration of transplant hospitalization, and need for rehospitalization. They used a multivariable regression model to evaluate associations between clinical and demographic variables and a positive screen for PTSD.
The median age of the 71 patients was 58 years; 61% were male. A preexisting diagnosis of depression was present in 25 patients (35%), their mean Model for End-Stage Liver Disease (MELD) score at time of transplant was 31, and their median time from transplant was 1,163 days. In all, nine patients (12.7%) tested positive for PTSD on the PCL-5, and all met criteria for a provisional diagnosis of PTSD based on the DSM-5 criteria. This prevalence is about two times higher than the prevalence of PTSD in the general population (6.7%), comparable with that reported for heart transplant recipients (10.8%) and coronary artery disease (9%), but lower than that reported for ICU patients (38%), HIV patients (35.3%), and in those with Crohn’s disease (19.1%).
On multivariable logistic regression, only three factors were found to be significantly associated with the development of PTSD: younger age at transplant (P = .019), history of depression (P = .008), and a history of PTSD (P less than .001). “What I found surprising was that the MELD score at the time of transplant and the number of readmissions or complications around the time of transplant were not predictive of PTSD,” Ms. O’Meara said.
One possible explanation for the finding of younger age being a predictor of PTSD, she continued, is that younger liver transplant patients may lack certain coping skills, compared with their older counterparts. “Maybe patients who have had more years to deal with their disease are more accepting of it and they learn how to use productive tools to manage it.”
In their abstract, the researchers acknowledged certain limitations of the study, including its cross-sectional design, small sample size, and lack of corresponding pretransplant data.
The researchers reported having no financial disclosures.
REPORTING FROM THE LIVER MEETING 2018
Key clinical point: Liver transplant recipients have a higher rate of PTSD than the general population and younger patients may be at a higher risk.
Major finding: In all, nine liver transplant patients (12.7%) tested positive for PTSD, which is about two times higher than the prevalence of PTSD in the general population (6.7%).
Study details: A cross-sectional analysis of 71 liver transplant recipients.
Disclosures: The researchers reported having no financial disclosures.
Novel acetaminophen hepatotoxicity strategy curbs inflammation
SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.
The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.
The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.
Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.
Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.
In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.
The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.
To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.
Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.
Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.
The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.
SOURCE: Liu J. AASLD 2018, Abstract 0040.
SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.
The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.
The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.
Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.
Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.
In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.
The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.
To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.
Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.
Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.
The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.
SOURCE: Liu J. AASLD 2018, Abstract 0040.
SAN FRANCISCO – A novel therapeutic strategy shows initial promise in dampening hepatic cell injury in mice caused by overexposure to acetaminophen. The approach relies on a synthetic version of heparan sulfate, which is believed to interfere with recruitment of neutrophils to the site of hepatic injury. That reduces harm caused by inflammation and may offer a longer therapeutic window than N-acetyl cysteine, which is the current standard therapy but is only effective if given within 8 hours of the injury.
The endogenous syndecan-1, which is a heparan sulfate, is also known to act as a native defense mechanism against inflammatory injury to hepatocytes. “It looks like heparan sulfate attenuates inflammatory responses,” said Jian Liu, PhD, during a presentation of his research at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Liu is a professor of chemical biology and medicinal chemistry at the University of North Carolina at Chapel Hill.
The heparan sulfate analogue heparin has long been used as an anticoagulant, of course, which suggests that a novel heparan sulfate has a good chance of also being safe.
Dr. Liu’s team had to identify a heparan sulfate that had a hepatoprotective effect, but a heparan sulfate’s unique biological activity depends on the specific pattern of sulfation on the heparan molecule. Heparans isolated from natural sources are generally a complex mixture, which makes them difficult to study and produce in large enough quantities to be therapeutically useful.
Dr. Liu’s team used a combinatory approach, harnessing various enzymes to produce hundreds of different heparan sulfate variants, and then screened them for hepatoprotective activity. That process identified an 18-chain heparan sulfate with hepatoprotective activity. With an active formula in hand, they could employ the enzymes to create enough of the pure compound to further the research. “It’s probably two to three hundred times more efficient than the traditional chemical synthesis,” said Dr. Liu.
In mice, researchers injected the 18-mer 30 minutes after a hepatotoxic dose of acetaminophen and again after 12 hours. Tissue staining showed less migration of neutrophils, as well as lower concentrations of tumor necrosis factor–alpha. The animals also had lower alanine transferase levels than did the untreated animals, as well as greater survival after 4 days.
The pathological process surrounding acetaminophen overdose involves release of the high mobility group box 1 (HMGB1) protein from necrotic hepatocytes, which in turn binds to the receptor for advanced glycation end-products (RAGE). The HMGB1/RAGE complex then binds to neutrophils, recruiting them to the site of the injury and initiating inflammation.
To better understand the molecule’s role in the pathological process, the researchers studied RAGE knockout mice, and found that the 18-mer had no protective effect in these animals, suggesting that it relies on RAGE for its biological activity.
Heparan sulfates are widely present in the body, which prompted the researchers to investigate their endogenous effect. In the liver, the primary heparan sulfate is syndecan-1. The researchers demonstrated that the molecule is shed from cell surfaces in response to acetaminophen toxicity and that the levels correlate with HMGB1 release.
Dr. Liu believes that syndecan-1 acts as a natural buffer to inflammation, helping to neutralize HMGB1 and limit damage. “The problem is that when the damage is massive, the shed of syndecan-1 is not enough,” said Dr. Liu. He hopes that something like his team’s heparan sulfate 18-mer can be used therapeutically to bolster these endogenous controls and prevent further damage.
The research was funded by Glycan Therapeutics. Dr. Liu founded Glycan, which offers custom-synthesized heparan sulfates and chondroitin sulfates for research purposes.
SOURCE: Liu J. AASLD 2018, Abstract 0040.
REPORTING FROM AASLD 2018
High rates of prescription opioid, benzodiazepine use observed in chronic liver disease
SAN FRANCISCO – .
“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.
In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.
Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.
“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.
She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.
Dr. Konerman reported having no financial disclosures.
SAN FRANCISCO – .
“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.
In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.
Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.
“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.
She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.
Dr. Konerman reported having no financial disclosures.
SAN FRANCISCO – .
“Middle-aged individuals and those with a background of substance abuse and mental health conditions appear to have highest rates of use and represent populations for which targeted interventions to curb use could be highest yield,” lead study author Monica Konerman, MD, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases.
In an effort to better understand the rates of prescription opioid and benzodiazepine use in chronic liver disease, Dr. Konerman, director of the Michigan Medicine NAFLD Clinic at the University of Michigan, Ann Arbor, and her colleagues drew from the Truven Health Analytics Marketscan databases from 2009 to 2015. They limited the analysis to individuals with drug coverage who had chronic hepatitis C (HCV) without cirrhosis, cirrhosis, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD), and examined pharmacy files for outpatient prescriptions.
Dr. Konerman reported data from 210,191 patients with HCV, 79,332 with cirrhosis, 766,840 with CHF, and 1,438,798 with COPD. Their median age was 59 years, and 51% were female. In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with CHF, and 24% among those with COPD. At the same time, in per person-years, the prevalence of benzodiazepine use was 12% among patients with chronic HCV, 21% among patients with cirrhosis, 12% among those with CHF, and 13% among those with COPD. Use of opioids was greatest in adults 40-59 years of age (P less than .001). High-dose opioid use, defined as 100 opioid morphine equivalents per day or greater, occurred in 23% of those with cirrhosis and in 22% of those with HCV.
“The significant increase in rates of use in chronic liver disease, compared to other chronic conditions was remarkable, particularly given that patients with liver disease are at higher risk for adverse consequences of use due to hepatic metabolism of these medications,” Dr. Konerman said.
She went on to acknowledge “inherent limitations to studies that are secondary database analyses that rely on diagnosis codes for categorization of disease with potential for both over and under classification. We also did not capture inpatient prescriptions,” she said.
Dr. Konerman reported having no financial disclosures.
REPORTING FROM THE LIVER MEETING 2018
Key clinical point: About one-fourth of patients with chronic hepatitis C use prescription opioids.
Major finding: In per person-years, the prevalence of prescription opioid use was 25% among patients with chronic HCV, 53% among patients with cirrhosis, 26% among those with congestive heart failure, and 24% among those with chronic obstructive pulmonary disease.
Study details: An analysis of 210,191 patients who had chronic hepatitis C.
Disclosures: Dr. Konerman reported having no financial disclosures.
U.S. death rates from chronic liver disease continue to rise
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
SAN FRANCISCO –
“I believe it’s all related to a big increase in obesity and type 2 diabetes in this country,” lead study author Zobair M. Younossi, MD, MPH, said in an interview in advance of the annual meeting of the American Association for the Study of Liver Diseases. “Those two risk factors drive NAFLD and its progressive type, nonalcoholic steatohepatitis (NASH). That accounts for at least part of the increase in mortality related to liver disease.”
In an effort to evaluate recent mortality trends in chronic liver disease in the United States, Dr. Younossi and his colleagues drew from National Vital Statistics Data during 2007-2016. They used ICD-10 codes to select mortality data for alcoholic liver disease, chronic hepatitis B and C, iron overload, NAFLD, cirrhosis, and hepatocellular carcinoma. NAFLD cases were defined as those having an ICD-10 code for NAFLD/NASH or an ICD-10 code for “cirrhosis of unknown etiology.” Next, the researchers adjusted age-standardized death rates to the 2000 U.S. Census population and used logistic regression and propensity scores to estimate predictors of chronic liver disease-related deaths.
Dr. Younossi, who chairs the department of medicine at Inova Fairfax Medical Campus, in Falls Church, Va., and his colleagues reported findings from 838,809 chronic liver disease–related deaths during the study period. They found that the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population in 2007 to 24.9/100,000 population in 2016, which translated into an annual percentage change of 1.3% for males and 2.5% for females. Chronic liver disease–related deaths increased with age and were highest among those aged 55-64 years, followed by those aged 65-74 years – an average annual percentage change of 3.4% and 3.1% in each group.
Among chronic liver disease–related deaths, the most common diagnostic etiology was NAFLD (34.7%), followed by alcoholic liver disease (28.8%) and chronic hepatitis C (21.1%). Between 2007 and 2016, death rates increased from 7.6 to 9.0 per 100,000 population for NAFLD (an average annual percentage change of 2.1%) and from 6.1 to 7.9 per 100,000 population for alcoholic liver disease (an average annual percentage change of 3.1%). “What surprised me was that, despite highly effective treatment for HCV, we still have a burden of hepatitis C in this country,” Dr. Younossi said. “It’s still the most common cause of liver disease in the U.S. But it seems like hepatitis C–related liver disease is being replaced quickly by liver disease from nonalcoholic steatohepatitis. This transition between hepatitis C as the most important cause of liver disease and liver mortality to NASH or obesity-related NASH is becoming more rapid than I expected.”
On multivariate analysis, three factors were independently associated with an increased risk of death in NAFLD: the presence of type 2 diabetes (odds ratio, 1.78), cardiovascular disease (OR, 1.07), and renal failure (OR, 1.08).
“One important message from this study is that NASH is very common in the U.S. population,” said Dr. Younossi, who is also a professor of medicine at Virginia Commonwealth University, Richmond. “These patients are underrecognized and underdiagnosed because they are asymptomatic. The second message is that there is a subtype of patients with fatty liver disease – even a subtype of NASH – that can progress to cirrhosis and its complications. We have to pay attention to this silent disease to identify patients who are at risk for progressive liver disease and try to address some of the risk issues, such as tight control of diabetes, obesity, and control of hypertension and hyperlipidemia. Short of that, right now we have very few medical treatments such as vitamin E and pioglitazone recommended for a very selected group. In contrast, there are plenty of new medications that are being developed. The first step in tackling this disease is to identify who the patients are with fatty liver disease who are at risk for bad outcomes and make sure they’re linked to care by a knowledgeable caregiver [who] understands the importance of NASH.”
Dr. Younossi acknowledged certain limitations of the study, including the fact that liver disease diagnoses were based on ICD-10 coding. He disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, BMS, AbbVie, Viking, Term Quest Diagnostics, Echosens,and Shionogi. He has also received grant/research support from Gilead, Intercept, and BMS.
Source: Hepatol. 2018;68[S1], Abstract 763.
AT THE LIVER MEETING 2018
Key clinical point: Nonalcoholic steatohepatitis is very common in the U.S. population.
Major finding: Between 2007 and 2016, the age-standardized death rate for chronic liver disease increased from 21.9/100,000 population to 24.9/100,000 population.
Study details: An analysis of 838,809 chronic liver disease–related deaths from 2007 to 2016.
Disclosures: Dr. Younossi disclosed that he is a consultant for Gilead, Intercept, Novo Nordisk, Bristol-Myers Squibb, AbbVie, Viking, Term Quest Diagnostics, Echosens, and Shionogi. He has also received grant/research support from Gilead, Intercept, and Bristol-Myers Squibb.
Source: Hepatol. 2018;68[S1], Abstract 763.
Norfloxacin might benefit patients with advanced cirrhosis and low ascites fluid protein levels
Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.
Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.
Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.
Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.
Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.
In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.
Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”
The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.
SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.
Prolonged antimicrobial use in patients with decompensated cirrhosis is an area of unclear mortality benefit and may actually increase risk in some patients given antimicrobial resistance. This randomized double-blind, placebo-controlled trial by Moreau et al. evaluates the mortality associated with long-term fluoroquinolone therapy in patients without indications for primary or secondary prophylaxis. Although the study had limited statistical power to detect clear benefit, the authors found that 6-month mortality was not reduced in patients with Child-Pugh class C cirrhosis who received treatment with daily oral fluoroquinolone therapy for 6 months. Subgroup analysis of individuals with ascites fluid total protein levels lower than 15 g/L showed a survival benefit at 6 months.
Determining quantifiable risk for known factors associated with liver disease mortality is a pressing issue, especially in the pretransplant setting where infectious risk is compounded post transplant with changes in gut flora, addition of potent immunosuppressants, and increased metabolic demands. Biologic measurements that correlate with increased complications and mortality, like low protein ascites, are helpful in complex clinical settings.Studying patients with advanced and decompensated liver disease in a systematic, longitudinal manner with any pharmacologic intervention is a particular challenge given the unpredictable nature of decompensation events and variable outcomes from those events. However, attempts to quantify risk and benefit even in this unpredictable patient population is worthwhile to stratify patients for interventions and minimize risk of liver-related and overall mortality – as well as peritransplant complications and posttransplant survival.
Julia J. Wattacheril, MD, MPH, is a physician- scientist and director of the Nonalcoholic Fatty Liver Disease Program in the Center for Liver Disease and Transplantation at Columbia University Irving Medical Center–New York Presbyterian Hospital, New York; an assistant professor, department of medicine, division of digestive and liver diseases at the Columbia University Vagelos College of Physicians and Surgeons. She has no conflicts.
Prolonged antimicrobial use in patients with decompensated cirrhosis is an area of unclear mortality benefit and may actually increase risk in some patients given antimicrobial resistance. This randomized double-blind, placebo-controlled trial by Moreau et al. evaluates the mortality associated with long-term fluoroquinolone therapy in patients without indications for primary or secondary prophylaxis. Although the study had limited statistical power to detect clear benefit, the authors found that 6-month mortality was not reduced in patients with Child-Pugh class C cirrhosis who received treatment with daily oral fluoroquinolone therapy for 6 months. Subgroup analysis of individuals with ascites fluid total protein levels lower than 15 g/L showed a survival benefit at 6 months.
Determining quantifiable risk for known factors associated with liver disease mortality is a pressing issue, especially in the pretransplant setting where infectious risk is compounded post transplant with changes in gut flora, addition of potent immunosuppressants, and increased metabolic demands. Biologic measurements that correlate with increased complications and mortality, like low protein ascites, are helpful in complex clinical settings.Studying patients with advanced and decompensated liver disease in a systematic, longitudinal manner with any pharmacologic intervention is a particular challenge given the unpredictable nature of decompensation events and variable outcomes from those events. However, attempts to quantify risk and benefit even in this unpredictable patient population is worthwhile to stratify patients for interventions and minimize risk of liver-related and overall mortality – as well as peritransplant complications and posttransplant survival.
Julia J. Wattacheril, MD, MPH, is a physician- scientist and director of the Nonalcoholic Fatty Liver Disease Program in the Center for Liver Disease and Transplantation at Columbia University Irving Medical Center–New York Presbyterian Hospital, New York; an assistant professor, department of medicine, division of digestive and liver diseases at the Columbia University Vagelos College of Physicians and Surgeons. She has no conflicts.
Prolonged antimicrobial use in patients with decompensated cirrhosis is an area of unclear mortality benefit and may actually increase risk in some patients given antimicrobial resistance. This randomized double-blind, placebo-controlled trial by Moreau et al. evaluates the mortality associated with long-term fluoroquinolone therapy in patients without indications for primary or secondary prophylaxis. Although the study had limited statistical power to detect clear benefit, the authors found that 6-month mortality was not reduced in patients with Child-Pugh class C cirrhosis who received treatment with daily oral fluoroquinolone therapy for 6 months. Subgroup analysis of individuals with ascites fluid total protein levels lower than 15 g/L showed a survival benefit at 6 months.
Determining quantifiable risk for known factors associated with liver disease mortality is a pressing issue, especially in the pretransplant setting where infectious risk is compounded post transplant with changes in gut flora, addition of potent immunosuppressants, and increased metabolic demands. Biologic measurements that correlate with increased complications and mortality, like low protein ascites, are helpful in complex clinical settings.Studying patients with advanced and decompensated liver disease in a systematic, longitudinal manner with any pharmacologic intervention is a particular challenge given the unpredictable nature of decompensation events and variable outcomes from those events. However, attempts to quantify risk and benefit even in this unpredictable patient population is worthwhile to stratify patients for interventions and minimize risk of liver-related and overall mortality – as well as peritransplant complications and posttransplant survival.
Julia J. Wattacheril, MD, MPH, is a physician- scientist and director of the Nonalcoholic Fatty Liver Disease Program in the Center for Liver Disease and Transplantation at Columbia University Irving Medical Center–New York Presbyterian Hospital, New York; an assistant professor, department of medicine, division of digestive and liver diseases at the Columbia University Vagelos College of Physicians and Surgeons. She has no conflicts.
Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.
Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.
Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.
Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.
Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.
In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.
Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”
The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.
SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.
Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.
Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.
Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.
Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.
Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.
In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.
Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”
The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.
SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.
FROM GASTROENTEROLOGY
Key clinical point: Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy, but norfloxacin did appear to benefit a subgroup of patients with low ascites fluid protein levels.
Major finding: Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93).
Study details: Multicenter double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy.
Disclosures: The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.
Source: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.
Crohn’s disease tied to anal canal high-risk HPV infection
Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.
High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.
Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.
The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.
A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.
Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).
Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.
The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.
SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.
Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.
High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.
Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.
The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.
A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.
Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).
Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.
The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.
SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.
Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.
High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.
Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.
The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.
A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.
Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).
Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.
The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.
SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Crohn’s disease was associated with high-risk human papillomavirus infection.
Major finding: High-risk HPV and HPV16 were detected in 30% of patients with Crohn’s disease versus 18% of those without Crohn’s disease (P = .005).
Study details: Analyses of anal tissue samples from 467 consecutive patients, including 70 with Crohn’s disease.
Disclosures: The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.
Source: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.
Length of stay, complications predict readmission for cirrhosis patients
PHILADELPHIA – Patients with cirrhosis have a higher risk of hospital readmission if their length of stay is less than 4 days, if they have cirrhosis-related complications, and if they are discharged to an extended-care facility or to home health care, according to a recent presentation at the annual meeting of the American College of Gastroenterology.
“The presence of cirrhosis-related complications is very strongly associated with readmissions,” Chandraprakash Umapathy, MD, MS, from the University of California, San Francisco, Fresno, said during his presentation. “Quality improvement efforts should focus on optimizing the management of complications of cirrhosis in the outpatient setting to reduce readmissions.”
In a retrospective cohort study, Dr. Umapathy and colleagues identified 230,036 patients from the Healthcare Cost and Utilization Project National Readmission Database for 2014 who had been discharged with a diagnosis of cirrhosis; of these patients, there were 185,737 index cases after excluding readmissions. Included patients had a mean age of 60.2 years and mean length of stay of 6.4 days, with 46% of patients having a length of stay longer than 4 days and mean total charges of $56,519. With regard to cirrhosis, 55% of patients displayed cirrhosis complications and 6.7% had more than three cirrhosis-related complications; the most common complication was ascites, in 32% of patients.
Overall, 11.09% of patients were readmitted at 30 days and 18.74% of patients were readmitted at 90 days, Dr. Umapathy said. Patients were more likely to be readmitted at 30 days if they were originally admitted on a weekend (adjusted prevalence ratio, 1.06; P = .001); into a medium (1.09; P = .009) or large (1.11; P less than .001) hospital; were admitted at a metropolitan teaching hospital (1.07; P less than .001); were insured by Medicaid (1.07; P less than .001); or were transferred to an extended care (1.51; P less than .001) facility or discharged to home health care (1.43; P less than .001).
Compared with patients who were not readmitted at 30 days, patients with 30-day readmission had a higher rate of alcoholic liver disease (43% vs. 46%; P less than .001), hepatitis C (28% vs. 32%; P less than .001), ascites (31% vs. 43%; P less than .001), hepatic encephalopathy (15% vs. 22%; P less than .001), hepatorenal syndrome (2.3% vs. 4.9%; P less than .001), hepatocellular cancer (5.1% vs. 5.7%; P = .001), presence of any cirrhosis complications (54% vs. 65%; P less than .001), and presence of more than three cirrhosis-related complications (6.3% vs. 10%; P less than .001). When adjusted in a multivariate analysis, association with readmission at 30 days for patients with cirrhosis-related complications such as ascites (1.42; P less than .001), hepatic encephalopathy (1.44; P less than .001), and hepatorenal syndrome (1.34; P less than .001) remained, Dr. Umapathy noted.
Length of stay longer than 4 days (0.84; P less than .001) and variceal hemorrhage (0.74; P = .002) were associated with reduced risk of readmissions at 30 days. “Focus on length of stay may result in patients being discharged prematurely, leading to higher early readmission,” Dr. Umapathy said.
Dr. Umapathy reports no relevant conflicts of interest.
SOURCE: Umapathy C et al. ACG 2018, Presentation 60
PHILADELPHIA – Patients with cirrhosis have a higher risk of hospital readmission if their length of stay is less than 4 days, if they have cirrhosis-related complications, and if they are discharged to an extended-care facility or to home health care, according to a recent presentation at the annual meeting of the American College of Gastroenterology.
“The presence of cirrhosis-related complications is very strongly associated with readmissions,” Chandraprakash Umapathy, MD, MS, from the University of California, San Francisco, Fresno, said during his presentation. “Quality improvement efforts should focus on optimizing the management of complications of cirrhosis in the outpatient setting to reduce readmissions.”
In a retrospective cohort study, Dr. Umapathy and colleagues identified 230,036 patients from the Healthcare Cost and Utilization Project National Readmission Database for 2014 who had been discharged with a diagnosis of cirrhosis; of these patients, there were 185,737 index cases after excluding readmissions. Included patients had a mean age of 60.2 years and mean length of stay of 6.4 days, with 46% of patients having a length of stay longer than 4 days and mean total charges of $56,519. With regard to cirrhosis, 55% of patients displayed cirrhosis complications and 6.7% had more than three cirrhosis-related complications; the most common complication was ascites, in 32% of patients.
Overall, 11.09% of patients were readmitted at 30 days and 18.74% of patients were readmitted at 90 days, Dr. Umapathy said. Patients were more likely to be readmitted at 30 days if they were originally admitted on a weekend (adjusted prevalence ratio, 1.06; P = .001); into a medium (1.09; P = .009) or large (1.11; P less than .001) hospital; were admitted at a metropolitan teaching hospital (1.07; P less than .001); were insured by Medicaid (1.07; P less than .001); or were transferred to an extended care (1.51; P less than .001) facility or discharged to home health care (1.43; P less than .001).
Compared with patients who were not readmitted at 30 days, patients with 30-day readmission had a higher rate of alcoholic liver disease (43% vs. 46%; P less than .001), hepatitis C (28% vs. 32%; P less than .001), ascites (31% vs. 43%; P less than .001), hepatic encephalopathy (15% vs. 22%; P less than .001), hepatorenal syndrome (2.3% vs. 4.9%; P less than .001), hepatocellular cancer (5.1% vs. 5.7%; P = .001), presence of any cirrhosis complications (54% vs. 65%; P less than .001), and presence of more than three cirrhosis-related complications (6.3% vs. 10%; P less than .001). When adjusted in a multivariate analysis, association with readmission at 30 days for patients with cirrhosis-related complications such as ascites (1.42; P less than .001), hepatic encephalopathy (1.44; P less than .001), and hepatorenal syndrome (1.34; P less than .001) remained, Dr. Umapathy noted.
Length of stay longer than 4 days (0.84; P less than .001) and variceal hemorrhage (0.74; P = .002) were associated with reduced risk of readmissions at 30 days. “Focus on length of stay may result in patients being discharged prematurely, leading to higher early readmission,” Dr. Umapathy said.
Dr. Umapathy reports no relevant conflicts of interest.
SOURCE: Umapathy C et al. ACG 2018, Presentation 60
PHILADELPHIA – Patients with cirrhosis have a higher risk of hospital readmission if their length of stay is less than 4 days, if they have cirrhosis-related complications, and if they are discharged to an extended-care facility or to home health care, according to a recent presentation at the annual meeting of the American College of Gastroenterology.
“The presence of cirrhosis-related complications is very strongly associated with readmissions,” Chandraprakash Umapathy, MD, MS, from the University of California, San Francisco, Fresno, said during his presentation. “Quality improvement efforts should focus on optimizing the management of complications of cirrhosis in the outpatient setting to reduce readmissions.”
In a retrospective cohort study, Dr. Umapathy and colleagues identified 230,036 patients from the Healthcare Cost and Utilization Project National Readmission Database for 2014 who had been discharged with a diagnosis of cirrhosis; of these patients, there were 185,737 index cases after excluding readmissions. Included patients had a mean age of 60.2 years and mean length of stay of 6.4 days, with 46% of patients having a length of stay longer than 4 days and mean total charges of $56,519. With regard to cirrhosis, 55% of patients displayed cirrhosis complications and 6.7% had more than three cirrhosis-related complications; the most common complication was ascites, in 32% of patients.
Overall, 11.09% of patients were readmitted at 30 days and 18.74% of patients were readmitted at 90 days, Dr. Umapathy said. Patients were more likely to be readmitted at 30 days if they were originally admitted on a weekend (adjusted prevalence ratio, 1.06; P = .001); into a medium (1.09; P = .009) or large (1.11; P less than .001) hospital; were admitted at a metropolitan teaching hospital (1.07; P less than .001); were insured by Medicaid (1.07; P less than .001); or were transferred to an extended care (1.51; P less than .001) facility or discharged to home health care (1.43; P less than .001).
Compared with patients who were not readmitted at 30 days, patients with 30-day readmission had a higher rate of alcoholic liver disease (43% vs. 46%; P less than .001), hepatitis C (28% vs. 32%; P less than .001), ascites (31% vs. 43%; P less than .001), hepatic encephalopathy (15% vs. 22%; P less than .001), hepatorenal syndrome (2.3% vs. 4.9%; P less than .001), hepatocellular cancer (5.1% vs. 5.7%; P = .001), presence of any cirrhosis complications (54% vs. 65%; P less than .001), and presence of more than three cirrhosis-related complications (6.3% vs. 10%; P less than .001). When adjusted in a multivariate analysis, association with readmission at 30 days for patients with cirrhosis-related complications such as ascites (1.42; P less than .001), hepatic encephalopathy (1.44; P less than .001), and hepatorenal syndrome (1.34; P less than .001) remained, Dr. Umapathy noted.
Length of stay longer than 4 days (0.84; P less than .001) and variceal hemorrhage (0.74; P = .002) were associated with reduced risk of readmissions at 30 days. “Focus on length of stay may result in patients being discharged prematurely, leading to higher early readmission,” Dr. Umapathy said.
Dr. Umapathy reports no relevant conflicts of interest.
SOURCE: Umapathy C et al. ACG 2018, Presentation 60
REPORTING FROM ACG 2018
Key clinical point: Cirrhosis-related complications and shorter length of stay were associated with higher rates of readmissions for patients with cirrhosis.
Major finding: 11.09% of patients were readmitted at 30 days and 18.74% of patients at 90 days, with the most common reasons for readmission including presence of cirrhosis complications and length of stay less than 4 days.
Study details: A retrospective cohort study of 185,737 index cases in the Healthcare Cost and Utilization Project National Readmission Database.
Disclosures: Dr. Umapathy reports no relevant conflicts of interest.
Source: Umapathy C et al. ACG 2018, Presentation 60.
Child-Pugh class does not affect HE recurrence in patients taking rifaximin
PHILADELPHIA – according to a recent presentation at the annual meeting of the American College of Gastroenterology.
Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.
“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.
Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.
In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.
Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.
With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.
“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.
This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.
SOURCE: Flamm SL et al ACG 2018, Presentation 58.
PHILADELPHIA – according to a recent presentation at the annual meeting of the American College of Gastroenterology.
Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.
“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.
Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.
In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.
Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.
With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.
“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.
This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.
SOURCE: Flamm SL et al ACG 2018, Presentation 58.
PHILADELPHIA – according to a recent presentation at the annual meeting of the American College of Gastroenterology.
Steven L. Flamm, MD, from Northwestern University, Chicago, and his colleagues examined results from a previous randomized, double-blinded trial of 140 patients receiving twice-daily rifaximin at 550 mg for 6 months in which the results showed rifaximin successfully maintained remission of hepatic encephalopathy (HE), compared with 159 patients receiving placebo.
“This pivotal study was published in March of 2010, but one of the post hoc assessments that was not performed was looking at various different phases of hepatic impairment as dictated by [Child-Pugh] class and each of those responses to this product,” Dr. Flamm said in his presentation.
Patients in the study were included if they had a Model For End-Stage Liver Disease score of 25 or less and two or more overt HE within 6 months (Conn score 1 or less) but were currently in remission. The researchers allowed the use of concomitant lactulose during the study period, which was used in 94.1% of rifaximin and 91.2% of placebo patients.
In the post hoc analysis, Dr. Flamm and his colleagues divided rifaximin and placebo patients into Child-Pugh class A (46 patients vs. 56 patients), class B (65 patients vs. 72 patients), and class C (17 patients vs. 14 patients) groups. For rifaximin and placebo patients, the mean age was 57.3 years and 57.2 years in the class A group, 54.4 years and 57.0 years in the class B group, and 56.1 years and 57.6 years in the class C group, respectively.
Overall, 8 of 46 rifaximin patients (17.4%) in the Child-Pugh class A and 15 of 65 rifaximin patients (23.1%) in the class B groups experienced an overt HE event during the 6-month study period, compared with 26 of 56 patients in the class A (46.4%) and 32 of 72 patients (44.4%) in the class B placebo groups; 5 of 17 rifaximin patients (29.4%) in the Child-Pugh class C group experienced their first overt HE event, compared with 9 of 14 (64.3%) patients in the placebo group.
With regard to first HE-related hospitalization, 5 of 46 patients (10.9%) in the rifaximin Child-Pugh class A group, 8 of 65 rifaximin patients (12.3%) in the class B group, and 4 of 17 rifaximin patients (23.5%) in the class C group experienced hospitalization because of HE, compared with 15 of 56 patients (23.2%) in the Child-Pugh class A group, 15 of 72 patients (20.8%) in the class B group, and 5 of 14 patients (35.7%) in the class C placebo group. The researchers noted lactulose use in the majority of patient cases in the study “provided further benefit” in reducing overt HE events.
“Although numeric differences were observed favoring rifaximin for the incidence of HE-related hospitalizations, a risk reduction versus placebo could not be firmly established, and presumably this was largely due to a lack of adequate power because of small sample size,” Dr. Flamm said.
This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors report advisory committee membership, board membership, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.
SOURCE: Flamm SL et al ACG 2018, Presentation 58.
REPORTING FROM ACG 2018
Key clinical point: Child-Pugh class does not significantly affect the overt hepatic encephalopathy recurrence rate in patients taking rifaximin, compared with placebo.
Major finding: A total of 17.4% of Child-Pugh class A, 23.1% of class B, and 29.4% class C patients taking rifaximin experienced overt hepatic encephalopathy, compared with 46.4% of Child-Pugh class A, 44.4% of class B, and 64.3% of class C patients receiving placebo.
Study details: A post hoc analysis of 299 patients receiving twice-daily rifaximin or placebo for 6 months.
Disclosures: This study and its analysis were supported by Salix Pharmaceuticals. Dr. Flamm and other coauthors reported advisory committee membership, board memberships, employment, or consultancy with AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck, and Salix Pharmaceuticals. One coauthor reported no relevant conflicts of interest.
Source: Flamm SL et al. ACG 2018, Presentation 58.
ACIP supports hepatitis A vaccine for homeless individuals
Homeless individuals aged 1 year and older should be vaccinated against hepatitis A, based on a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“It is important that we take a national approach to vaccinating homeless” people, Noele Nelson, MD, PhD, MPH, of the CDC’s Division of Viral Hepatitis, said in a presentation prior to the vote, in which all 11 committee members voted in favor of hepatitis A vaccination for the homeless population.
Even limited vaccination will increase the herd immunity of the homeless population over time, she said.
Dr. Nelson presented data on the pros and cons of routine hepatitis A vaccination for homeless individuals aged 1 year and older. The Hepatitis Vaccines Work Group convened four meetings in advance of the October ACIP meeting and reached a consensus that homelessness is an independent indication for hepatitis A vaccination, she said.
If the hepatitis A vaccine is included as an ACIP recommendation, “it is more likely to be considered by homeless service providers,” noted Dr. Nelson. She also cited a low quality of evidence for adverse events associated with hepatitis A vaccination.
The work group considerations in the wake of a nationwide hepatitis A outbreak earlier in 2018 included the challenges of controlling outbreaks, which can spread quickly among the homeless population because of poor personal hygiene, limited sanitation, and tight living quarters. These factors make the homeless population more reliant on a vaccine for protection. An outbreak in San Diego, Calif., in particular, occurred largely in the homeless population.
“Routine vaccination is a more feasible approach to reach the homeless over time through regular homeless care providers,” Dr. Nelson said. As for costs, integrating vaccination into routine care for the homeless is cheaper and much less disruptive than the cost of responding to an outbreak.
The “cons” of recommending routine hepatitis A vaccination for the homeless population included the challenges of administrative record keeping. However, during the public comment period, Mae Morgan, MD, an internist who is medical director of Mercy Care Decatur Street & City of Refuge in Atlanta, emphasized that local homeless care organizations have procedures to manage routine vaccination. “If anyone is concerned that there is not a network in place, there are health centers to do this [that] would implement the vaccine.”
The ACIP committee members had no financial conflicts to disclose.
Homeless individuals aged 1 year and older should be vaccinated against hepatitis A, based on a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“It is important that we take a national approach to vaccinating homeless” people, Noele Nelson, MD, PhD, MPH, of the CDC’s Division of Viral Hepatitis, said in a presentation prior to the vote, in which all 11 committee members voted in favor of hepatitis A vaccination for the homeless population.
Even limited vaccination will increase the herd immunity of the homeless population over time, she said.
Dr. Nelson presented data on the pros and cons of routine hepatitis A vaccination for homeless individuals aged 1 year and older. The Hepatitis Vaccines Work Group convened four meetings in advance of the October ACIP meeting and reached a consensus that homelessness is an independent indication for hepatitis A vaccination, she said.
If the hepatitis A vaccine is included as an ACIP recommendation, “it is more likely to be considered by homeless service providers,” noted Dr. Nelson. She also cited a low quality of evidence for adverse events associated with hepatitis A vaccination.
The work group considerations in the wake of a nationwide hepatitis A outbreak earlier in 2018 included the challenges of controlling outbreaks, which can spread quickly among the homeless population because of poor personal hygiene, limited sanitation, and tight living quarters. These factors make the homeless population more reliant on a vaccine for protection. An outbreak in San Diego, Calif., in particular, occurred largely in the homeless population.
“Routine vaccination is a more feasible approach to reach the homeless over time through regular homeless care providers,” Dr. Nelson said. As for costs, integrating vaccination into routine care for the homeless is cheaper and much less disruptive than the cost of responding to an outbreak.
The “cons” of recommending routine hepatitis A vaccination for the homeless population included the challenges of administrative record keeping. However, during the public comment period, Mae Morgan, MD, an internist who is medical director of Mercy Care Decatur Street & City of Refuge in Atlanta, emphasized that local homeless care organizations have procedures to manage routine vaccination. “If anyone is concerned that there is not a network in place, there are health centers to do this [that] would implement the vaccine.”
The ACIP committee members had no financial conflicts to disclose.
Homeless individuals aged 1 year and older should be vaccinated against hepatitis A, based on a unanimous vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
“It is important that we take a national approach to vaccinating homeless” people, Noele Nelson, MD, PhD, MPH, of the CDC’s Division of Viral Hepatitis, said in a presentation prior to the vote, in which all 11 committee members voted in favor of hepatitis A vaccination for the homeless population.
Even limited vaccination will increase the herd immunity of the homeless population over time, she said.
Dr. Nelson presented data on the pros and cons of routine hepatitis A vaccination for homeless individuals aged 1 year and older. The Hepatitis Vaccines Work Group convened four meetings in advance of the October ACIP meeting and reached a consensus that homelessness is an independent indication for hepatitis A vaccination, she said.
If the hepatitis A vaccine is included as an ACIP recommendation, “it is more likely to be considered by homeless service providers,” noted Dr. Nelson. She also cited a low quality of evidence for adverse events associated with hepatitis A vaccination.
The work group considerations in the wake of a nationwide hepatitis A outbreak earlier in 2018 included the challenges of controlling outbreaks, which can spread quickly among the homeless population because of poor personal hygiene, limited sanitation, and tight living quarters. These factors make the homeless population more reliant on a vaccine for protection. An outbreak in San Diego, Calif., in particular, occurred largely in the homeless population.
“Routine vaccination is a more feasible approach to reach the homeless over time through regular homeless care providers,” Dr. Nelson said. As for costs, integrating vaccination into routine care for the homeless is cheaper and much less disruptive than the cost of responding to an outbreak.
The “cons” of recommending routine hepatitis A vaccination for the homeless population included the challenges of administrative record keeping. However, during the public comment period, Mae Morgan, MD, an internist who is medical director of Mercy Care Decatur Street & City of Refuge in Atlanta, emphasized that local homeless care organizations have procedures to manage routine vaccination. “If anyone is concerned that there is not a network in place, there are health centers to do this [that] would implement the vaccine.”
The ACIP committee members had no financial conflicts to disclose.
FROM AN ACIP MEETING
Aspirin cuts risk of liver and ovarian cancer
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
FROM JAMA ONCOLOGY
Key clinical point: Regular aspirin use was associated with a decreased risk of ovarian cancer and hepatocellular carcinoma.
Major finding: Low-dose aspirin was associated with a 23% lower risk of ovarian cancer and a 49% reduced risk of developing hepatocellular carcinoma.
Study details: The hepatocellular carcinoma study was a population-based study of two nationwide, prospective cohorts of 87,507 men and 45,864 women; the ovarian cancer study was a cohort study using data from two prospective cohorts, with 93,664 people in one and 111,834 in the other.
Disclosures: The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The hepatocellular carcinoma study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
Sources: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.