From the AGA Journals

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

Adding an immune modulator (IM) to anti–tumor necrosis factor (anti-TNF) initiation therapy benefits patients with Crohn’s disease (CD) but not those with ulcerative colitis (UC), according to a recent retrospective look at more than 1,000 cases.

The study showed that patients with CD who started combination therapy instead of monotherapy had lower rates of treatment ineffectiveness, experienced longer delays until hospitalization, and less often needed to switch their anti-TNF agent, reported lead author Laura E. Targownik, MD, of the University of Manitoba, in Winnipeg, Canada, and colleagues.

“Current guidelines on the medical management of IBD strongly support the use of IMs and anti-TNFs in combination over anti-TNF monotherapy,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, there is a sparsity of real-world data demonstrating the incremental benefits of combination therapy.”

The investigators noted that the SONIC trial, conducted in 2010, showed that patients treated with combination therapy were more likely to achieve corticosteroid-free remission at weeks 26 and 50; this became the basis of evidence leading multiple clinical guidelines to recommend combination therapy for patients with CD.

The present study involved 852 patients with CD and 303 with UC who began treatment with an anti-TNF agent during 2001-2016. Data were drawn from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database.

The main outcome of interest was treatment ineffectiveness, which was defined by any of the following four events: acute, IBD-related hospital admission for more than 48 hours; resective intestinal surgery; corticosteroid use at least 14 days after initiating anti-TNF therapy, or, if corticosteroids were used within 16 weeks of anti-TNF initiation, then subsequent corticosteroid use occurring at least 16 weeks after initiation; or switching to a different anti-TNF agent. The investigators also looked for differences in effectiveness between two agents from each class: anti-TNF agents infliximab and adalimumab, and immunomodulators methotrexate and azathioprine.

Results showed that patients with CD had higher rates of ineffectiveness-free survival when treated with combination therapy instead of monotherapy at 1 year (74.2% vs. 68.6%) and 2 years (64.0% vs. 54.5%). Using a Cox proportional hazards model, this translated to a 38% reduced risk of treatment ineffectiveness (adjusted hazard ratio, 0.62).

“This suggests that the findings of the SONIC trial may extend to real-world clinical practice, even in patients who had previous IM exposure,” the investigators noted.

Combination therapy was also significantly associated with longer time to first IBD-related hospitalization (HR, 0.53) and the need to switch anti-TNF agent (HR, 0.63). However, no such relationships were found for time to resective surgery or corticosteroid use. Although combination therapy had no impact on the rate of primary treatment ineffectiveness in multivariable logistic regression, those who received anti-TNF therapy for more than 90 days had delayed secondary treatment ineffectiveness and fewer IBD-related hospitalizations. Choice of agent from either class had no influence on effectiveness of combination therapy.

In contrast with the above findings, combination therapy in patients with UC was less promising, which aligns with previous studies.

“[W]e were not able to demonstrate a significant advantage to combination therapy in persons with UC,” the investigators wrote. “In addition, all published cohort studies to date have not been able to confirm a significant benefit to combination therapy in UC. ... In light of the lower quality of prior evidence, combined with the results from our study, the indication for combination therapy in UC would appear to be weaker.”

“Further analyses in larger cohorts may clarify whether there is a clinically relevant benefit of combination therapy in persons with UC,” the investigators concluded. “Because of the discrepancy between our findings and those of a meta-analysis of cohort studies previously published on this topic, confirmation of our results is required in future studies.”

The investigators disclosed no funding or conflicts of interest.

SOURCE: Targownik LE et al. Clin Gastroenterol Hepatol. 2018 Nov 15. doi: 10.1016/j.cgh.2018.11.003.

Endoscopists who described themselves as “compulsive” and “thorough” had significantly higher rates of adenoma detection, according to results from a self-reported survey of 117 physician endoscopists.

Financial incentives, malpractice concerns, and perceptions of adenoma detection rate as a quality metric were not associated with endoscopists’ detection rates in the survey.

“Adenoma detection rates were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals,” Ghideon Ezaz, MD, of Beth Israel Deaconess Medical Center in Boston and associates wrote in Clinical Gastroenterology and Hepatology.

These feelings were related to withdrawal times rather than daily procedure volume. “We hypothesize that performing a meticulous examination is mentally taxing and can cause a physician to feel rushed or perceive that it is difficult to keep pace or accomplish goals,” the researchers wrote.

Adenoma detection rates vary widely among physicians – up to threefold in some studies. Researchers have failed to attribute most of this discrepancy to seemingly obvious factors such as the type of specialty training an endoscopist completes. The traditional fee-for-service payment model is likely a culprit since physicians are paid for performing as many colonoscopies as possible rather than for procedural quality. Other potential variables include personality traits and endoscopists’ knowledge and views on the importance of adenoma detection rates.

To examine the roles of these factors in adenoma detection rates, Dr. Ezaz and coinvestigators used electronic health records data from four health systems in Boston, Pittsburgh, North Carolina, and Seattle. Detection rates were adjusted to control for differences among patient populations. Next, the researchers surveyed the physicians who performed the endoscopies about their financial motivations, knowledge and perceptions of colonoscopy quality, and personality traits.

Among 117 physicians surveyed, the median risk-adjusted adenoma detection rate was 29.3%, with an interquartile range of 24.1%-35.5%. “We found no significant association between adenoma detection rate and financial incentives, malpractice concerns, or physicians’ perceptions of adenoma detection rate as a quality metric,” the researchers wrote.

In contrast, endoscopists who described themselves as either much or somewhat more compulsive than their peers had significantly higher median adjusted rates of adenoma detection than did endoscopists who described themselves as about the same or somewhat less compulsive than others. These adenoma detection rates, in respective order, were 33.1%, 32.9%, 26.4%, and 27.3% (P = .0019). Adenoma detection rates also were significantly higher among physicians who described themselves as more thorough than their peers, who said they felt rushed during endoscopy, and who reported having difficulty pacing themselves, accomplishing goals, or managing unforeseen situations.

A secondary analysis revealed the same links between personality traits and adenomas per colonoscopy. The findings support an expert’s prior assertion (Gastrointest Endosc. 2007 Jan;65[1]:145-50) that the best endoscopists are “slow, careful, and compulsive,” the researchers noted. They recommended nurturing “meticulousness and attention to detail” during training and evaluating trainees based on these characteristics.

The National Cancer Institute provided funding. The researchers reported having no conflicts of interest.
 

SOURCE: Ezaz G et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.019.

Endoscopists who described themselves as “compulsive” and “thorough” had significantly higher rates of adenoma detection, according to results from a self-reported survey of 117 physician endoscopists.

Financial incentives, malpractice concerns, and perceptions of adenoma detection rate as a quality metric were not associated with endoscopists’ detection rates in the survey.

“Adenoma detection rates were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals,” Ghideon Ezaz, MD, of Beth Israel Deaconess Medical Center in Boston and associates wrote in Clinical Gastroenterology and Hepatology.

These feelings were related to withdrawal times rather than daily procedure volume. “We hypothesize that performing a meticulous examination is mentally taxing and can cause a physician to feel rushed or perceive that it is difficult to keep pace or accomplish goals,” the researchers wrote.

Adenoma detection rates vary widely among physicians – up to threefold in some studies. Researchers have failed to attribute most of this discrepancy to seemingly obvious factors such as the type of specialty training an endoscopist completes. The traditional fee-for-service payment model is likely a culprit since physicians are paid for performing as many colonoscopies as possible rather than for procedural quality. Other potential variables include personality traits and endoscopists’ knowledge and views on the importance of adenoma detection rates.

To examine the roles of these factors in adenoma detection rates, Dr. Ezaz and coinvestigators used electronic health records data from four health systems in Boston, Pittsburgh, North Carolina, and Seattle. Detection rates were adjusted to control for differences among patient populations. Next, the researchers surveyed the physicians who performed the endoscopies about their financial motivations, knowledge and perceptions of colonoscopy quality, and personality traits.

Among 117 physicians surveyed, the median risk-adjusted adenoma detection rate was 29.3%, with an interquartile range of 24.1%-35.5%. “We found no significant association between adenoma detection rate and financial incentives, malpractice concerns, or physicians’ perceptions of adenoma detection rate as a quality metric,” the researchers wrote.

In contrast, endoscopists who described themselves as either much or somewhat more compulsive than their peers had significantly higher median adjusted rates of adenoma detection than did endoscopists who described themselves as about the same or somewhat less compulsive than others. These adenoma detection rates, in respective order, were 33.1%, 32.9%, 26.4%, and 27.3% (P = .0019). Adenoma detection rates also were significantly higher among physicians who described themselves as more thorough than their peers, who said they felt rushed during endoscopy, and who reported having difficulty pacing themselves, accomplishing goals, or managing unforeseen situations.

A secondary analysis revealed the same links between personality traits and adenomas per colonoscopy. The findings support an expert’s prior assertion (Gastrointest Endosc. 2007 Jan;65[1]:145-50) that the best endoscopists are “slow, careful, and compulsive,” the researchers noted. They recommended nurturing “meticulousness and attention to detail” during training and evaluating trainees based on these characteristics.

The National Cancer Institute provided funding. The researchers reported having no conflicts of interest.
 

SOURCE: Ezaz G et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.019.

Endoscopists who described themselves as “compulsive” and “thorough” had significantly higher rates of adenoma detection, according to results from a self-reported survey of 117 physician endoscopists.

Financial incentives, malpractice concerns, and perceptions of adenoma detection rate as a quality metric were not associated with endoscopists’ detection rates in the survey.

“Adenoma detection rates were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals,” Ghideon Ezaz, MD, of Beth Israel Deaconess Medical Center in Boston and associates wrote in Clinical Gastroenterology and Hepatology.

These feelings were related to withdrawal times rather than daily procedure volume. “We hypothesize that performing a meticulous examination is mentally taxing and can cause a physician to feel rushed or perceive that it is difficult to keep pace or accomplish goals,” the researchers wrote.

Adenoma detection rates vary widely among physicians – up to threefold in some studies. Researchers have failed to attribute most of this discrepancy to seemingly obvious factors such as the type of specialty training an endoscopist completes. The traditional fee-for-service payment model is likely a culprit since physicians are paid for performing as many colonoscopies as possible rather than for procedural quality. Other potential variables include personality traits and endoscopists’ knowledge and views on the importance of adenoma detection rates.

To examine the roles of these factors in adenoma detection rates, Dr. Ezaz and coinvestigators used electronic health records data from four health systems in Boston, Pittsburgh, North Carolina, and Seattle. Detection rates were adjusted to control for differences among patient populations. Next, the researchers surveyed the physicians who performed the endoscopies about their financial motivations, knowledge and perceptions of colonoscopy quality, and personality traits.

Among 117 physicians surveyed, the median risk-adjusted adenoma detection rate was 29.3%, with an interquartile range of 24.1%-35.5%. “We found no significant association between adenoma detection rate and financial incentives, malpractice concerns, or physicians’ perceptions of adenoma detection rate as a quality metric,” the researchers wrote.

In contrast, endoscopists who described themselves as either much or somewhat more compulsive than their peers had significantly higher median adjusted rates of adenoma detection than did endoscopists who described themselves as about the same or somewhat less compulsive than others. These adenoma detection rates, in respective order, were 33.1%, 32.9%, 26.4%, and 27.3% (P = .0019). Adenoma detection rates also were significantly higher among physicians who described themselves as more thorough than their peers, who said they felt rushed during endoscopy, and who reported having difficulty pacing themselves, accomplishing goals, or managing unforeseen situations.

A secondary analysis revealed the same links between personality traits and adenomas per colonoscopy. The findings support an expert’s prior assertion (Gastrointest Endosc. 2007 Jan;65[1]:145-50) that the best endoscopists are “slow, careful, and compulsive,” the researchers noted. They recommended nurturing “meticulousness and attention to detail” during training and evaluating trainees based on these characteristics.

The National Cancer Institute provided funding. The researchers reported having no conflicts of interest.
 

SOURCE: Ezaz G et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.019.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Inflammatory bowel disease (IBD) treatment remains a challenge in part because care is often fragmented among providers in different specialties, according to the American Gastroenterological Association. To address the need for provider coordination, the AGA has issued a new referral pathway for IBD care, published in Gastroenterology.

“The goal of this pathway is to offer guidance to primary care, emergency department, and gastroenterology providers, by helping identify patients at risk of or diagnosed with IBD and provide direction on initiating appropriate patient referrals,” wrote lead author Jami Kinnucan, MD, of the University of Michigan, Ann Arbor, and members of the AGA workgroup.

In particular, the pathway focuses on gaps in IBD care related to inflammatory issues, mental health, and nutrition. The work group included not only gastroenterologists, but also a primary care physician, mental/behavioral health specialist, registered dietitian/nutritionist, critical care specialist, nurse practitioner, physician group representative, and a patient advocacy representative.

The pathway identifies the top three areas where IBD patients usually present with symptoms: the emergency department, primary care office, and gastroenterology office.

The work group developed a list of key characteristics associated with increased morbidity, established IBD, or IBD-related complications that can be separated into high-risk, moderate-risk, and low-risk groups to help clinicians determine the timing of and need for referrals.

The pathway uses a sample patient presenting with GI symptoms such as bloody diarrhea; GI bleeding; anemia; fecal urgency; fever; abdominal pain; weight loss; and pain, swelling, or redness in the joints. Clinicians then apply the key characteristics to triage the patients into the risk groups.

High-risk characteristics include history of perianal or severe rectal disease, or deep ulcers in the GI mucosa; two or more emergency department visits for GI problems within the past 6 months, severe anemia, inadequate response to outpatient IBD therapy, history of IBD-related surgery, and malnourishment.

Moderate-risk characteristics include anemia without clinical symptoms, chronic corticosteroid use, and no emergency department or other GI medical visits within the past year.

Low-risk characteristics include chronic narcotic use, one or more comorbidities (such as heart failure, active hepatitis B, oncologic malignancy, lupus, GI infections, primary sclerosing cholangitis, viral hepatitis, and celiac disease), one or more relevant mental health conditions (such as depression, anxiety, or chronic pain), and nonadherence to IBD medical therapies.

“Referrals should be based on the highest level of risk present, in the event that a patient has characteristics that fall in more than one risk category,” the work group wrote.

To further guide clinicians in referring patients with possible or diagnosed IBD to gastroenterology specialists and to mental health and nutrition specialists, the work group developed an IBD Characteristics Assessment Checklist and a Referral Feedback form to accompany the pathway.

The checklist is designed for use by any health care professional to help identify whether a patient needs to be referred based on the key characteristics; the feedback form gives gastroenterologists a template to communicate with referring physicians about comanagement strategies for the patient.

The pathway also includes more details on how clinicians can tackle barriers to mental health and nutrition care for IBD patients.

“Until further evaluations are conducted, the work group encourages the immediate use of the pathway to begin addressing the needed improvements for IBD care coordination and communication between the different IBD providers,” the authors wrote.

Dr. Kinnucan disclosed serving as a consultant for AbbVie, Janssen, and Pfizer and serving on the Patient Education Committee of the Crohn’s and Colitis Foundation.

SOURCE: Kinnucan J et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.064.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Among patients with moderate to severe ulcerative colitis, a median of 1.4 years and up to 4.4 years of tofacitinib therapy was safe apart from a dose-related increase in risk of herpes zoster infection, according to an integrated analysis of data from five clinical trials.

clsgraphics/iStockphoto

Compared with placebo, a 5-mg twice-daily maintenance dose of tofacitinib (Xeljanz) produced a 2.1-fold greater risk of herpes zoster infection (95% confidence interval, 0.4-6.0), while a 10-mg, twice-daily dose produced a statistically significant 6.6-fold increase in incidence (95% CI, 3.2-12.2).

With the exception of the higher incidence rate of herpes zoster, “in the overall cohort, the safety profile of tofacitinib was generally similar to that of tumor necrosis factor inhibitor therapies,” wrote William J. Sandborn, MD, director of the inflammatory bowel disease center and professor of medicine, at the University of California, San Diego, and associates. The findings were published in Clinical Gastroenterology and Hepatology.

Tofacitinib is an oral, small-molecular Janus kinase inhibitor approved in the United States for treating moderate to severe ulcerative colitis, as well as rheumatoid and psoriatic arthritis. The recommended ulcerative colitis dose is 10 mg twice daily for at least 8 weeks (induction therapy) followed by 5 or 10 mg twice daily (maintenance). The safety of tofacitinib has been studied in patients with rheumatoid arthritis through 9 years of treatment. To begin a similar undertaking in ulcerative colitis, Dr. Sandborn and associates pooled data from three 8-week, double-blind, placebo-controlled induction trials, as well as one 52-week, double-blind, placebo-controlled maintenance trial and one ongoing open-label trial. All patients received twice-daily tofacitinib (5 mg or 10 mg) or placebo.

Among 1,157 tofacitinib recipients in the pooled analysis, 84% received an average of 10 mg twice daily. For every 100 person-years of tofacitinib exposure, there were an estimated 2.0 serious infections, 1.3 opportunistic infections, 4.1 herpes zoster infections, 1.4 malignancies (including nonmelanoma skin cancer, which had an incidence of 0.7), 0.2 major adverse cardiovascular events, and 0.2 gastrointestinal perforations. The likelihood of these events did not increase with time on tofacitinib, the researchers said.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

Obesity promotes the localization of inducible nitric oxide synthase (iNOS) in hepatic lysosomes, leading to a cascade of downstream effects that include excess lysosomal nitric oxide production, reduced hepatic autophagy, and insulin resistance, investigators reported.

“It is well known that in the context of obesity, chronic inflammation and lysosome dysfunction coexist in the liver,” wrote Qingwen Qian, PhD, of the University of Iowa in Iowa City and associates in Cellular and Molecular Gastroenterology and Hepatology. “Our studies suggest that lysosomal iNOS-mediated nitric oxide signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.” They noted that the findings could hasten the development of new treatments for metabolic diseases.

Lysosomes recycle autophagocytosed intracellular and extracellular material, which is crucial to maintain several types of homeostasis within the liver. Each hepatocyte has about 250 lysosomes, which help regulate nutrient sensing, glycogen metabolism, cholesterol trafficking, and viral defense.

Activation of iNOS is a hallmark of inflammation, and iNOS levels are known to be elevated in the livers of patients with hepatitis C, alcoholic cirrhosis, and alpha 1-anti-trypsin disorder, the researchers wrote. “At the cellular level, iNOS produces pathological nitric oxide [NO], which triggers downstream effects, such as aberrant S-nitrosylation. These downstream effects can disrupt the function of organelles such as the mitochondria and the endoplasmic reticulum.”

Studies indicate that pathologic NO impairs lysosomal function in neurodegenerative diseases, cardiovascular disease, nonalcoholic fatty liver disease, and kidney disease, Dr. Qian and associates noted. But it was unclear whether NO in hepatocytes was generated by local iNOS or localized to lysosomes.

The researchers therefore studied cell cultures of primary murine hepatocytes by measuring their lysosomal activity, autophagy levels, and NO levels. They also studied a murine model of diet-induced obesity in which 60% of calories were from fat. They performed glucose tolerance tests by means of intraperitoneal glucose injections and studied the effects of insulin infusion. Finally, they performed immunohistology, immunohistochemistry, electron microscopy, and measurements of nitrosylated proteins and lysosomal arginine in frozen liver sections from the mice. Lysosomal arginine is required to catalyze NO production in the setting of inflammation as observed in obesity. In fact, concomitant stimulation of lysosomal arginine transport and activation of mTOR (an enzyme which tightly regulates transcription factor EB) was sufficient to stimulate lysosomal NO production in hepatocytes even in the absence of an inflammatory stimulus; pointing to a central role for these processes.

The researchers found that a NO scavenger diminished lysosomal NO production, while overexpression of both mTOR and a lysomal arginine transporter upregulated lysosomal NO production and suppressed autophagy. In mice with diet-induced obesity, deleting iNOS also improved nitrosative stress in hepatic lysosomes, promoted lysosomal biogenesis by activating transcription factor EB, enhanced lysosomal function and autophagy, and improved hepatic insulin sensitivity. Improved insulin sensitivity diminished, however, when the researchers suppressed transcription factor EB or autophagy-related 7 (Atg7).

Usually, iNOS is primarily expressed in hepatic Kupffer cells, but obesity increases the expression of iNOS in hepatocytes, which promotes hepatic insulin resistance and inflammation, the researchers commented. Unpublished data indicate that deleting iNOS initially protects against obesity-linked fatty liver steatosis and insulin resistance, but that these benefits weaken over time. “Nevertheless, our data showed that liver-specific iNOS suppression has a protective role,” they wrote. “Specifically, we showed that iNOS inactivates transcription factor EB, and that suppression of transcription factor EB and Atg7 diminishes the improved hepatic insulin sensitivity by iNOS deletion.” Transcription factor EB both regulates autophagy and is a “key player in lipid metabolism,” they added. It remains unclear whether the metabolic effects of iNOS solely relate to autophagy, they noted.

Funders included the American Heart Association, American Diabetes Association, and National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Qingwen Qian, et al. Cell Molec Gastroenterol Hepatol. 2019;8(1):95-110.
 

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

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After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

Fuse/Thinkstock

After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

For adults with Crohn’s disease in remission at baseline, eating red and processed meat no more than once per month did not reduce risk of relapse in a randomized control trial.

Fuse/Thinkstock

After 49 weeks, there were no significant differences in time to relapse, time to moderate or severe relapse, or time to persistent relapse between the low- and high-meat groups, reported Lindsey G. Aldenberg, DO, of the Children’s Hospital of Philadelphia and coinvestigators. The findings were published in Gastroenterology.

The randomized study included 213 adults with Crohn’s disease whose short Crohn’s Disease Activity Index (sCDAI) score was 150 or less at baseline and who consumed red meat at least once weekly. They were instructed to consume one serving (3 ounces) of red meat or any processed (smoked, salted, or otherwise preserved) meat at least twice weekly (high-meat group) or no more than once monthly (low-meat group). To create a placebo-like effect, all patients were told to drink at least 16 ounces of water daily. Each week, patients were emailed a web-based survey of disease status and dietary adherence. At baseline and during six other weeks, they also received a daily survey of disease activity and current medications. The primary outcome was symptomatic relapse, defined as at least a 70-point rise such that sCDAI score exceeded 150, surgery for Crohn’s disease flare, or self-reported initiation or dose increase of mesalamine, thiopurine, methotrexate, corticosteroid, anti–tumor necrosis factor-alpha therapy, or natalizumab.

In all, 78% (166) of patients either completed the study or experienced an outcome. Symptomatic relapse occurred in 62% of these 166 patients, while 42% and 35% had moderate to severe or persistent relapses, respectively. “There were no significant differences in time to relapse for any of the outcomes (P greater than .3 for all outcomes),” the researchers wrote. Results were similar when they assumed that patients who completed no surveys all relapsed at week 1.

At week 20, median fecal calprotectin levels were higher in the high-meat arm (74.5 mcg/g) than in the low-meat arm (36.0 mcg/g), but the difference was not statistically significant. Proportions of patients with fecal calprotectin levels above 150 or 250 mcg/g also did not significantly differ between arms.

Adherence to the diets was reasonable: Patients in the high-meat group reported consuming at least two servings of red or processed meat during 98.5% of weeks, while patients in the low-meat arm completely abstained from red or processed meat during 57.3% of weeks. A logistic regression model showed that the high-meat group was much more likely to consume a least two servings of red or processed meat in the prior week than the low-meat group (P less than .0001). Approximately 90% of patients in both arms drank the recommended amount of water.

Study participants were part of IBD Partners, an Internet-based cohort of more than 15,000 patients with inflammatory bowel disease. Recruitment into the trial occurred through emails, social media, educational and fundraising events, and the Crohn’s & Colitis Foundation website, the researchers said.

“Based on these results, there is insufficient evidence to recommend reduction of red and processed meat consumption solely for the purpose of improving Crohn’s disease outcomes, although there may be some benefit for other health conditions,” Dr. Aldenberg and associates concluded.

The Crohn’s and Colitis Foundation and the National Institutes of Health supported the work. Dr. Aldenberg disclosed receiving research funding from Seres Therapeutics. Two of six coinvestigators disclosed ties to Nestle Health Science, AbbVie, Pfizer, Eli Lilly, and several other pharmaceutical companies.

SOURCE: Aldenberg L et al. Gastroenterology. 2019 Mar 11. doi: 10.1053/j.gastro.2019.03.01.

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

Tumor specimens from 17% of patients with pancreatic ductal adenocarcinomas contained genomic alterations for which targeted therapies exist, researchers reported in Gastroenterology.

“We identified mutations in genes that could contribute to progression of intraductal papillary mucinous neoplasms into malignancies. These alterations might be used as biomarkers for early detection,” wrote Aatur D. Singhi, MD, PhD, of the University of Pittsburgh and associates.

The most common genomic mutations in pancreatic ductal adenocarcinoma (PDAC) involve KRAS, TP53, CDKN2A, and SMAD4, none of which can be treated by currently approved targeted agents. But PDACs are genomically very heterogeneous and contain low levels (less than 5%) of many other mutations, the researchers noted. In small studies, these low-prevalence mutations included kinase gene amplifications and rearrangements, which may be useful as treatment targets or predictive biomarkers of response.

To further characterize PDAC mutations and their relative penetrance, the researchers performed targeted genomic profile analyses of 3,594 PDAC tumor specimens from an international cohort. The tests included capture-based targeted genomic profiling of up to 315 cancer-linked genes and the intron regions of 28 genes that are rearranged in cancer cells. The researchers classified genomic alterations based on published signaling pathways, including receptor tyrosine kinase/ras/mitogen-activated protein kinase (RTK/ras/MAPK) activation, DNA damage repair, cell cycle control, transforming growth factor beta signaling, histone modification, switching/sucrose nonfermenting complex, phosphoinositide 3-kinase/mammalian target of rapamycin signaling, Wnt/beta-catenin pathway, RNA splicing, Notch pathway, angiogenesis, and hedgehog signaling. In addition, they analyzed tumor mutation burden in 1,021 samples and microsatellite instability status in 2,563 samples.

In all, the samples contained 19,120 genomic alterations of 317 genes. A total of 608 (17%) specimens harbored mutations considered actionable targets. These involved either the RTK/ras/MAPK signaling or DNA damage repair pathways. As expected, KRAS mutations were most common, but their penetrance (88%) was lower than in prior studies. This might be because the current study covered both resectable and nonresectable PDACs, while past studies tended to focus on resected PDACs only, the researchers said. Importantly, the 12% of KRAS wild-type PDACs often harbored other potentially targetable alterations of genes in the RTK/ras/MAPK pathway, such as kinase fusion, amplification, missense mutations, and intragenic-in-frame deletions.

A total of 81% of samples contained alterations of TP53 or other genes involved in DNA damage repair. Reflecting prior studies, the penetrance of individual DNA damage repair mutations was low – usually less than 5%. Most germline mutations involved the BRCA-FANC DNA repair pathway, and these may be targetable with agents such as poly (ADP-ribose) polymerase inhibitors and DNA strand-damaging, platinum-based cytotoxic regimens, the investigators wrote.

Among 3,117 samples with clinicopathologic data, 51% were from the primary tumor and the rest were from distal metastases of the liver, lung, nonregional lymph nodes, peritoneum, omentum, and other sites. Not surprisingly, BRCA1 and BRCA2 mutations were more common in younger patients, but KRAS, SMAD4, DNMT3A, and AP mutations were more common in older patients, and mutational frequencies also varied by sex, primary versus metastatic tumor status, and site of metastasis.

“The complex genomic heterogeneity in otherwise histologically similar PDACs suggests a one-size-fits-all approach to treating patients will not be successful,” they concluded. “Targeted genomic profiling of known genomic alterations across multiple tumor types highlights potentially targetable and predictive biomarkers for treatment in a significant subset of PDACs.”

Funders included the Pancreatic Cancer Action Network, the National Pancreas Foundation, and the Sky Foundation. Dr. Singhi and two coinvestigators reported receiving honoraria from Foundation Medicine, and seven other coinvestigators reported employment by and stock ownership in Foundation Medicine. No other disclosures were reported.

SOURCE: Singhi AD et al. Gastroenterology. 2019 Mar 2. doi: 10.1053/j.gastro.2019.02.03.

Tumor specimens from 17% of patients with pancreatic ductal adenocarcinomas contained genomic alterations for which targeted therapies exist, researchers reported in Gastroenterology.

“We identified mutations in genes that could contribute to progression of intraductal papillary mucinous neoplasms into malignancies. These alterations might be used as biomarkers for early detection,” wrote Aatur D. Singhi, MD, PhD, of the University of Pittsburgh and associates.

The most common genomic mutations in pancreatic ductal adenocarcinoma (PDAC) involve KRAS, TP53, CDKN2A, and SMAD4, none of which can be treated by currently approved targeted agents. But PDACs are genomically very heterogeneous and contain low levels (less than 5%) of many other mutations, the researchers noted. In small studies, these low-prevalence mutations included kinase gene amplifications and rearrangements, which may be useful as treatment targets or predictive biomarkers of response.

To further characterize PDAC mutations and their relative penetrance, the researchers performed targeted genomic profile analyses of 3,594 PDAC tumor specimens from an international cohort. The tests included capture-based targeted genomic profiling of up to 315 cancer-linked genes and the intron regions of 28 genes that are rearranged in cancer cells. The researchers classified genomic alterations based on published signaling pathways, including receptor tyrosine kinase/ras/mitogen-activated protein kinase (RTK/ras/MAPK) activation, DNA damage repair, cell cycle control, transforming growth factor beta signaling, histone modification, switching/sucrose nonfermenting complex, phosphoinositide 3-kinase/mammalian target of rapamycin signaling, Wnt/beta-catenin pathway, RNA splicing, Notch pathway, angiogenesis, and hedgehog signaling. In addition, they analyzed tumor mutation burden in 1,021 samples and microsatellite instability status in 2,563 samples.

In all, the samples contained 19,120 genomic alterations of 317 genes. A total of 608 (17%) specimens harbored mutations considered actionable targets. These involved either the RTK/ras/MAPK signaling or DNA damage repair pathways. As expected, KRAS mutations were most common, but their penetrance (88%) was lower than in prior studies. This might be because the current study covered both resectable and nonresectable PDACs, while past studies tended to focus on resected PDACs only, the researchers said. Importantly, the 12% of KRAS wild-type PDACs often harbored other potentially targetable alterations of genes in the RTK/ras/MAPK pathway, such as kinase fusion, amplification, missense mutations, and intragenic-in-frame deletions.

A total of 81% of samples contained alterations of TP53 or other genes involved in DNA damage repair. Reflecting prior studies, the penetrance of individual DNA damage repair mutations was low – usually less than 5%. Most germline mutations involved the BRCA-FANC DNA repair pathway, and these may be targetable with agents such as poly (ADP-ribose) polymerase inhibitors and DNA strand-damaging, platinum-based cytotoxic regimens, the investigators wrote.

Among 3,117 samples with clinicopathologic data, 51% were from the primary tumor and the rest were from distal metastases of the liver, lung, nonregional lymph nodes, peritoneum, omentum, and other sites. Not surprisingly, BRCA1 and BRCA2 mutations were more common in younger patients, but KRAS, SMAD4, DNMT3A, and AP mutations were more common in older patients, and mutational frequencies also varied by sex, primary versus metastatic tumor status, and site of metastasis.

“The complex genomic heterogeneity in otherwise histologically similar PDACs suggests a one-size-fits-all approach to treating patients will not be successful,” they concluded. “Targeted genomic profiling of known genomic alterations across multiple tumor types highlights potentially targetable and predictive biomarkers for treatment in a significant subset of PDACs.”

Funders included the Pancreatic Cancer Action Network, the National Pancreas Foundation, and the Sky Foundation. Dr. Singhi and two coinvestigators reported receiving honoraria from Foundation Medicine, and seven other coinvestigators reported employment by and stock ownership in Foundation Medicine. No other disclosures were reported.

SOURCE: Singhi AD et al. Gastroenterology. 2019 Mar 2. doi: 10.1053/j.gastro.2019.02.03.

Tumor specimens from 17% of patients with pancreatic ductal adenocarcinomas contained genomic alterations for which targeted therapies exist, researchers reported in Gastroenterology.

“We identified mutations in genes that could contribute to progression of intraductal papillary mucinous neoplasms into malignancies. These alterations might be used as biomarkers for early detection,” wrote Aatur D. Singhi, MD, PhD, of the University of Pittsburgh and associates.

The most common genomic mutations in pancreatic ductal adenocarcinoma (PDAC) involve KRAS, TP53, CDKN2A, and SMAD4, none of which can be treated by currently approved targeted agents. But PDACs are genomically very heterogeneous and contain low levels (less than 5%) of many other mutations, the researchers noted. In small studies, these low-prevalence mutations included kinase gene amplifications and rearrangements, which may be useful as treatment targets or predictive biomarkers of response.

To further characterize PDAC mutations and their relative penetrance, the researchers performed targeted genomic profile analyses of 3,594 PDAC tumor specimens from an international cohort. The tests included capture-based targeted genomic profiling of up to 315 cancer-linked genes and the intron regions of 28 genes that are rearranged in cancer cells. The researchers classified genomic alterations based on published signaling pathways, including receptor tyrosine kinase/ras/mitogen-activated protein kinase (RTK/ras/MAPK) activation, DNA damage repair, cell cycle control, transforming growth factor beta signaling, histone modification, switching/sucrose nonfermenting complex, phosphoinositide 3-kinase/mammalian target of rapamycin signaling, Wnt/beta-catenin pathway, RNA splicing, Notch pathway, angiogenesis, and hedgehog signaling. In addition, they analyzed tumor mutation burden in 1,021 samples and microsatellite instability status in 2,563 samples.

In all, the samples contained 19,120 genomic alterations of 317 genes. A total of 608 (17%) specimens harbored mutations considered actionable targets. These involved either the RTK/ras/MAPK signaling or DNA damage repair pathways. As expected, KRAS mutations were most common, but their penetrance (88%) was lower than in prior studies. This might be because the current study covered both resectable and nonresectable PDACs, while past studies tended to focus on resected PDACs only, the researchers said. Importantly, the 12% of KRAS wild-type PDACs often harbored other potentially targetable alterations of genes in the RTK/ras/MAPK pathway, such as kinase fusion, amplification, missense mutations, and intragenic-in-frame deletions.

A total of 81% of samples contained alterations of TP53 or other genes involved in DNA damage repair. Reflecting prior studies, the penetrance of individual DNA damage repair mutations was low – usually less than 5%. Most germline mutations involved the BRCA-FANC DNA repair pathway, and these may be targetable with agents such as poly (ADP-ribose) polymerase inhibitors and DNA strand-damaging, platinum-based cytotoxic regimens, the investigators wrote.

Among 3,117 samples with clinicopathologic data, 51% were from the primary tumor and the rest were from distal metastases of the liver, lung, nonregional lymph nodes, peritoneum, omentum, and other sites. Not surprisingly, BRCA1 and BRCA2 mutations were more common in younger patients, but KRAS, SMAD4, DNMT3A, and AP mutations were more common in older patients, and mutational frequencies also varied by sex, primary versus metastatic tumor status, and site of metastasis.

“The complex genomic heterogeneity in otherwise histologically similar PDACs suggests a one-size-fits-all approach to treating patients will not be successful,” they concluded. “Targeted genomic profiling of known genomic alterations across multiple tumor types highlights potentially targetable and predictive biomarkers for treatment in a significant subset of PDACs.”

Funders included the Pancreatic Cancer Action Network, the National Pancreas Foundation, and the Sky Foundation. Dr. Singhi and two coinvestigators reported receiving honoraria from Foundation Medicine, and seven other coinvestigators reported employment by and stock ownership in Foundation Medicine. No other disclosures were reported.

SOURCE: Singhi AD et al. Gastroenterology. 2019 Mar 2. doi: 10.1053/j.gastro.2019.02.03.

Infections during the first year of life were a significant risk factor for inflammatory bowel disease throughout the lifespan but especially prior to the age of 10 years, according to the findings of a large population-based study.

It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.

IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.

Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.

Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.

Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.

“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.

The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.

SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.

Infections during the first year of life were a significant risk factor for inflammatory bowel disease throughout the lifespan but especially prior to the age of 10 years, according to the findings of a large population-based study.

It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.

IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.

Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.

Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.

Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.

“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.

The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.

SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.

Infections during the first year of life were a significant risk factor for inflammatory bowel disease throughout the lifespan but especially prior to the age of 10 years, according to the findings of a large population-based study.

It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.

IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.

Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.

Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.

Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.

“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.

The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.

SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.

Achieving sustained virologic response to direct-acting antiviral therapy for chronic hepatitis C virus infection cuts lifetime hepatocellular carcinoma risk by approximately 70%, even when patients have baseline cirrhosis, experts wrote in Gastroenterology.

When used after curative-intent treatment for hepatocellular carcinoma, direct-acting antiviral (DAA) therapy also does not appear to make recurrent cancer more probable or more aggressive, wrote Amit G. Singal, MD, and associates in an American Gastroenterological Association clinical practice update. Studies that compared DAA therapy with either interferon-based therapy or no treatment have found “similar if not lower recurrence than the comparator groups,” they wrote. Rather, hepatocellular carcinoma is in itself highly recurrent: “While surgical resection and local ablative therapies are considered curative, [probability of] recurrence approaches 25%-35% within the first year, and 50%-60% within 2 years.”

Direct-acting antiviral therapy for chronic hepatitis C infection improves several aspects of liver health, but experts have debated whether and how these benefits affect the risk and behavior of hepatocellular carcinoma. To explore the issue, Dr. Singal, medical director of the liver tumor program and clinical chief of hepatology at UT Southwestern Medical Center in Dallas and associates reviewed published clinical trials, observational studies, and systematic reviews. Among 11 studies of more than 3,000 patients in five countries, sustained virologic response (SVR) to DAA therapy was associated with about a 70% reduction in the risk of liver cancer, even after adjustment for clinical and demographic variables. “The relative reduction is similar in patients with and without cirrhosis,” the experts wrote.

Since patients with fibrosis (F3) or cirrhosis are at highest risk for hepatocellular carcinoma, they should undergo baseline imaging and remain under indefinite post-SVR surveillance as long as they are eligible for potentially curative treatment, the practice update states. The experts recommended twice-yearly ultrasound, with or without serum alpha-fetoprotein, noting that current evidence supports neither shorter surveillance intervals nor alternative imaging modalities.

“The presence of active hepatocellular carcinoma is associated with a small but statistically significant decrease in SVR with DAA therapy,” the experts confirmed, based on the results of three studies. They recommended that, when possible, patients with hepatocellular carcinoma first receive curative-intent treatment, such as with liver resection or ablation. Direct-acting antiviral therapy can begin 4-6 months later, once there has been time to confirm response to hepatocellular carcinoma treatment.

For patients who are listed for liver transplantation, timing of DAA therapy “should be determined on a case-by-case basis with consideration of median wait times for the region, availability of HCV-positive organs, and degree of liver dysfunction,” they added. “For example, DAA therapy may be beneficial pretransplant for patients in regions with long wait times or limited hepatitis C virus–positive donor organ availability, whereas therapy may be delayed until posttransplant in regions with shorter wait times or a high proportion of hepatitis C virus–positive donor organs that would otherwise go unused.”

For patients with active intermediate or advanced liver cancer, it remains unclear whether DAA therapy is usually worth the costs and risks, they noted. This is because the likelihood of complete response is lower and the competing risk of death is higher than in patients with earlier-stage hepatocellular carcinoma. Pending further data, they recommend basing the decision on patients’ preferences, tumor burden, degree of liver dysfunction, and life expectancy. At their institutions, the researchers do not treat patients with DAA therapy unless their life expectancy exceeds 2 years.

The experts disclosed research funding from the National Cancer Institute, U.S. Veterans Administration, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Singal reported personal fees or research funding from AbbVie, Bayer, Bristol-Myers Squibb, Eisai, Exact Sciences, Exelixis, Gilead, Glycotest, Roche, and Wako Diagnostics. His coauthors disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Conatus, Genfit, Gilead, Intercept, and Merck.

SOURCE: Singal AG et al. Gastroenterology. 2019 Mar 13. doi: 10.1053/j.gastro.2019.02.046.

Achieving sustained virologic response to direct-acting antiviral therapy for chronic hepatitis C virus infection cuts lifetime hepatocellular carcinoma risk by approximately 70%, even when patients have baseline cirrhosis, experts wrote in Gastroenterology.

When used after curative-intent treatment for hepatocellular carcinoma, direct-acting antiviral (DAA) therapy also does not appear to make recurrent cancer more probable or more aggressive, wrote Amit G. Singal, MD, and associates in an American Gastroenterological Association clinical practice update. Studies that compared DAA therapy with either interferon-based therapy or no treatment have found “similar if not lower recurrence than the comparator groups,” they wrote. Rather, hepatocellular carcinoma is in itself highly recurrent: “While surgical resection and local ablative therapies are considered curative, [probability of] recurrence approaches 25%-35% within the first year, and 50%-60% within 2 years.”

Direct-acting antiviral therapy for chronic hepatitis C infection improves several aspects of liver health, but experts have debated whether and how these benefits affect the risk and behavior of hepatocellular carcinoma. To explore the issue, Dr. Singal, medical director of the liver tumor program and clinical chief of hepatology at UT Southwestern Medical Center in Dallas and associates reviewed published clinical trials, observational studies, and systematic reviews. Among 11 studies of more than 3,000 patients in five countries, sustained virologic response (SVR) to DAA therapy was associated with about a 70% reduction in the risk of liver cancer, even after adjustment for clinical and demographic variables. “The relative reduction is similar in patients with and without cirrhosis,” the experts wrote.

Since patients with fibrosis (F3) or cirrhosis are at highest risk for hepatocellular carcinoma, they should undergo baseline imaging and remain under indefinite post-SVR surveillance as long as they are eligible for potentially curative treatment, the practice update states. The experts recommended twice-yearly ultrasound, with or without serum alpha-fetoprotein, noting that current evidence supports neither shorter surveillance intervals nor alternative imaging modalities.

“The presence of active hepatocellular carcinoma is associated with a small but statistically significant decrease in SVR with DAA therapy,” the experts confirmed, based on the results of three studies. They recommended that, when possible, patients with hepatocellular carcinoma first receive curative-intent treatment, such as with liver resection or ablation. Direct-acting antiviral therapy can begin 4-6 months later, once there has been time to confirm response to hepatocellular carcinoma treatment.

For patients who are listed for liver transplantation, timing of DAA therapy “should be determined on a case-by-case basis with consideration of median wait times for the region, availability of HCV-positive organs, and degree of liver dysfunction,” they added. “For example, DAA therapy may be beneficial pretransplant for patients in regions with long wait times or limited hepatitis C virus–positive donor organ availability, whereas therapy may be delayed until posttransplant in regions with shorter wait times or a high proportion of hepatitis C virus–positive donor organs that would otherwise go unused.”

For patients with active intermediate or advanced liver cancer, it remains unclear whether DAA therapy is usually worth the costs and risks, they noted. This is because the likelihood of complete response is lower and the competing risk of death is higher than in patients with earlier-stage hepatocellular carcinoma. Pending further data, they recommend basing the decision on patients’ preferences, tumor burden, degree of liver dysfunction, and life expectancy. At their institutions, the researchers do not treat patients with DAA therapy unless their life expectancy exceeds 2 years.

The experts disclosed research funding from the National Cancer Institute, U.S. Veterans Administration, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Singal reported personal fees or research funding from AbbVie, Bayer, Bristol-Myers Squibb, Eisai, Exact Sciences, Exelixis, Gilead, Glycotest, Roche, and Wako Diagnostics. His coauthors disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Conatus, Genfit, Gilead, Intercept, and Merck.

SOURCE: Singal AG et al. Gastroenterology. 2019 Mar 13. doi: 10.1053/j.gastro.2019.02.046.

Achieving sustained virologic response to direct-acting antiviral therapy for chronic hepatitis C virus infection cuts lifetime hepatocellular carcinoma risk by approximately 70%, even when patients have baseline cirrhosis, experts wrote in Gastroenterology.

When used after curative-intent treatment for hepatocellular carcinoma, direct-acting antiviral (DAA) therapy also does not appear to make recurrent cancer more probable or more aggressive, wrote Amit G. Singal, MD, and associates in an American Gastroenterological Association clinical practice update. Studies that compared DAA therapy with either interferon-based therapy or no treatment have found “similar if not lower recurrence than the comparator groups,” they wrote. Rather, hepatocellular carcinoma is in itself highly recurrent: “While surgical resection and local ablative therapies are considered curative, [probability of] recurrence approaches 25%-35% within the first year, and 50%-60% within 2 years.”

Direct-acting antiviral therapy for chronic hepatitis C infection improves several aspects of liver health, but experts have debated whether and how these benefits affect the risk and behavior of hepatocellular carcinoma. To explore the issue, Dr. Singal, medical director of the liver tumor program and clinical chief of hepatology at UT Southwestern Medical Center in Dallas and associates reviewed published clinical trials, observational studies, and systematic reviews. Among 11 studies of more than 3,000 patients in five countries, sustained virologic response (SVR) to DAA therapy was associated with about a 70% reduction in the risk of liver cancer, even after adjustment for clinical and demographic variables. “The relative reduction is similar in patients with and without cirrhosis,” the experts wrote.

Since patients with fibrosis (F3) or cirrhosis are at highest risk for hepatocellular carcinoma, they should undergo baseline imaging and remain under indefinite post-SVR surveillance as long as they are eligible for potentially curative treatment, the practice update states. The experts recommended twice-yearly ultrasound, with or without serum alpha-fetoprotein, noting that current evidence supports neither shorter surveillance intervals nor alternative imaging modalities.

“The presence of active hepatocellular carcinoma is associated with a small but statistically significant decrease in SVR with DAA therapy,” the experts confirmed, based on the results of three studies. They recommended that, when possible, patients with hepatocellular carcinoma first receive curative-intent treatment, such as with liver resection or ablation. Direct-acting antiviral therapy can begin 4-6 months later, once there has been time to confirm response to hepatocellular carcinoma treatment.

For patients who are listed for liver transplantation, timing of DAA therapy “should be determined on a case-by-case basis with consideration of median wait times for the region, availability of HCV-positive organs, and degree of liver dysfunction,” they added. “For example, DAA therapy may be beneficial pretransplant for patients in regions with long wait times or limited hepatitis C virus–positive donor organ availability, whereas therapy may be delayed until posttransplant in regions with shorter wait times or a high proportion of hepatitis C virus–positive donor organs that would otherwise go unused.”

For patients with active intermediate or advanced liver cancer, it remains unclear whether DAA therapy is usually worth the costs and risks, they noted. This is because the likelihood of complete response is lower and the competing risk of death is higher than in patients with earlier-stage hepatocellular carcinoma. Pending further data, they recommend basing the decision on patients’ preferences, tumor burden, degree of liver dysfunction, and life expectancy. At their institutions, the researchers do not treat patients with DAA therapy unless their life expectancy exceeds 2 years.

The experts disclosed research funding from the National Cancer Institute, U.S. Veterans Administration, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Singal reported personal fees or research funding from AbbVie, Bayer, Bristol-Myers Squibb, Eisai, Exact Sciences, Exelixis, Gilead, Glycotest, Roche, and Wako Diagnostics. His coauthors disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Conatus, Genfit, Gilead, Intercept, and Merck.

SOURCE: Singal AG et al. Gastroenterology. 2019 Mar 13. doi: 10.1053/j.gastro.2019.02.046.