From the AGA Journals

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Use of clip closure significantly reduced delayed bleeding in patients who underwent resections for large colorectal lesions, based on data from 235 individuals.

Source: American Gastroenterological Association

“Closure of a mucosal defect with clips after resection has long been considered to reduce the risk of bleeding,” but evidence to support this practice is limited, wrote Eduardo Albéniz, MD, of the Public University of Navarra (Spain), and colleagues.

In a study published in Gastroenterology, the researchers identified 235 consecutive patients who had resections of large nonpedunculated colorectal lesions from May 2016 to June 2018. Patients had an average or high risk of delayed bleeding and were randomized to receive scar closure with either 11-mm through-the-scope clips (119 patients) or no clip (116 patients).

Delayed bleeding occurred in 14 control patients (12.1%), compared with 6 clip patients (5%), for a risk reduction of 7%. The clip group included 68 cases (57%) of complete closure and 33 cases (28%) with partial closure, as well as 18 cases of failure to close (15%); only 1 case of delayed bleeding occurred in the clip group after completion of clip closure. On average, six clips were needed for complete closure.

None of the patients who experienced delayed bleeding required surgical or angiographic intervention, although 15 of the 20 patients with bleeding underwent additional endoscopy. Other adverse events included immediate bleeding in 21 clip patients and 18 controls that was managed with snare soft-tip coagulation. No deaths were reported in connection with the study.

Demographics were similar between the two groups, but the subset of patients with complete closure included more individuals aged 75 years and older and more cases with smaller polyps, compared with other subgroups, the researchers noted.

The study findings were limited by several factors, including the difficulty in predicting delayed bleeding, the potential for selection bias given the timing of patient randomization, the lack of information about polyps that were excluded from treatment, and the difficulty in completely closing the mucosal defects, the researchers noted. However, the results suggest that complete clip closure, despite its challenges, “displays a clear trend to reduce delayed bleeding risk,” and is worth an attempt.

The study was supported by the Spanish Society of Digestive Endoscopy. The researchers had no financial conflicts to disclose. MicroTech (Nanjing, China) contributed the clips used in the study.

SOURCE: Albéniz E et al. Gastroenterology. 2019 Jul 27. doi: 10.1053/j.gastro.2019.07.037.

Use of clip closure significantly reduced delayed bleeding in patients who underwent resections for large colorectal lesions, based on data from 235 individuals.

Source: American Gastroenterological Association

“Closure of a mucosal defect with clips after resection has long been considered to reduce the risk of bleeding,” but evidence to support this practice is limited, wrote Eduardo Albéniz, MD, of the Public University of Navarra (Spain), and colleagues.

In a study published in Gastroenterology, the researchers identified 235 consecutive patients who had resections of large nonpedunculated colorectal lesions from May 2016 to June 2018. Patients had an average or high risk of delayed bleeding and were randomized to receive scar closure with either 11-mm through-the-scope clips (119 patients) or no clip (116 patients).

Delayed bleeding occurred in 14 control patients (12.1%), compared with 6 clip patients (5%), for a risk reduction of 7%. The clip group included 68 cases (57%) of complete closure and 33 cases (28%) with partial closure, as well as 18 cases of failure to close (15%); only 1 case of delayed bleeding occurred in the clip group after completion of clip closure. On average, six clips were needed for complete closure.

None of the patients who experienced delayed bleeding required surgical or angiographic intervention, although 15 of the 20 patients with bleeding underwent additional endoscopy. Other adverse events included immediate bleeding in 21 clip patients and 18 controls that was managed with snare soft-tip coagulation. No deaths were reported in connection with the study.

Demographics were similar between the two groups, but the subset of patients with complete closure included more individuals aged 75 years and older and more cases with smaller polyps, compared with other subgroups, the researchers noted.

The study findings were limited by several factors, including the difficulty in predicting delayed bleeding, the potential for selection bias given the timing of patient randomization, the lack of information about polyps that were excluded from treatment, and the difficulty in completely closing the mucosal defects, the researchers noted. However, the results suggest that complete clip closure, despite its challenges, “displays a clear trend to reduce delayed bleeding risk,” and is worth an attempt.

The study was supported by the Spanish Society of Digestive Endoscopy. The researchers had no financial conflicts to disclose. MicroTech (Nanjing, China) contributed the clips used in the study.

SOURCE: Albéniz E et al. Gastroenterology. 2019 Jul 27. doi: 10.1053/j.gastro.2019.07.037.

Use of clip closure significantly reduced delayed bleeding in patients who underwent resections for large colorectal lesions, based on data from 235 individuals.

Source: American Gastroenterological Association

“Closure of a mucosal defect with clips after resection has long been considered to reduce the risk of bleeding,” but evidence to support this practice is limited, wrote Eduardo Albéniz, MD, of the Public University of Navarra (Spain), and colleagues.

In a study published in Gastroenterology, the researchers identified 235 consecutive patients who had resections of large nonpedunculated colorectal lesions from May 2016 to June 2018. Patients had an average or high risk of delayed bleeding and were randomized to receive scar closure with either 11-mm through-the-scope clips (119 patients) or no clip (116 patients).

Delayed bleeding occurred in 14 control patients (12.1%), compared with 6 clip patients (5%), for a risk reduction of 7%. The clip group included 68 cases (57%) of complete closure and 33 cases (28%) with partial closure, as well as 18 cases of failure to close (15%); only 1 case of delayed bleeding occurred in the clip group after completion of clip closure. On average, six clips were needed for complete closure.

None of the patients who experienced delayed bleeding required surgical or angiographic intervention, although 15 of the 20 patients with bleeding underwent additional endoscopy. Other adverse events included immediate bleeding in 21 clip patients and 18 controls that was managed with snare soft-tip coagulation. No deaths were reported in connection with the study.

Demographics were similar between the two groups, but the subset of patients with complete closure included more individuals aged 75 years and older and more cases with smaller polyps, compared with other subgroups, the researchers noted.

The study findings were limited by several factors, including the difficulty in predicting delayed bleeding, the potential for selection bias given the timing of patient randomization, the lack of information about polyps that were excluded from treatment, and the difficulty in completely closing the mucosal defects, the researchers noted. However, the results suggest that complete clip closure, despite its challenges, “displays a clear trend to reduce delayed bleeding risk,” and is worth an attempt.

The study was supported by the Spanish Society of Digestive Endoscopy. The researchers had no financial conflicts to disclose. MicroTech (Nanjing, China) contributed the clips used in the study.

SOURCE: Albéniz E et al. Gastroenterology. 2019 Jul 27. doi: 10.1053/j.gastro.2019.07.037.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Direct-acting antiviral (DAA) therapy significantly reduced the risk of death in patients with hepatitis C infections and a history of hepatocellular carcinoma, based on data from 797 individuals.

Previous studies have reported a benefit of direct-acting antiviral (DAA) therapy for reducing mortality in patients with hepatocellular carcinoma (HCC), but data on its impact in patients with complete responses to HCC therapy are limited, wrote Amit G. Singal, MD, of the University of Texas, Dallas, and colleagues.

In a study published in Gastroenterology, the researchers identified adult HCC patients who achieved complete treatment response between January 2013 and December 2017. The study included patients from 31 locations in the United States and Canada. Complete response to treatment was defined as “disappearance of arterial enhancement from all HCC lesions on contrast-enhanced cross-sectional imaging.”

A total of 383 (48.1%) of patients were randomized to DAA therapy, and 414 (51.9%) did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy.

A total of 43 deaths occurred among DAA patients over 941 person-years of follow-up, compared with 103 deaths over 527 person-years of follow-up for the untreated controls. Overall, DAA therapy was associated with a significantly reduced risk of death (hazard ratio, 0.54), compared with no therapy. Of note, patients with a sustained virologic response showed a reduced risk of death (HR, 0.29), but those without a sustained virologic response to DAA therapy did not (HR, 1.13).

The findings support those from previous studies suggesting that DAA therapy may reduce mortality in patients with a history of HCC, the researchers said.

The study findings were limited by several factors, including potential confounding if DAA was given to patients with better prognoses, the researchers noted. Other limitations include the use of imaging in routine clinical care rather than centralized review, the loss of approximately 9% of the patients to follow-up, and the lack of data on hepatic decompensation during follow-up, the researchers said. However, the results were strengthened by the multicenter design, large cohort, and inclusion of untreated controls, and support the use of DAA therapies as “likely beneficial in HCV-infected patients with a history of HCC,” they concluded.

The study was funded in part by the National Cancer Institute and AbbVie. Dr. Singal disclosed relationships with companies including AbbVie, Gilead, Bayer, Eisai, Wako Diagnostics, Exact Sciences, Exelixis, Roche, Glycotest, and Bristol-Myers Squibb.

SOURCE: Singal AG et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.07.040.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

Help your patients understand what do expect during and how to prepare for a colonoscopy by sharing AGA’s patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/colonoscopy.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

Help your patients understand what do expect during and how to prepare for a colonoscopy by sharing AGA’s patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/colonoscopy.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

Screening for colorectal cancer in patients with cystic fibrosis is cost effective, and should be started at a younger age and performed more often, new research suggests.

While colorectal cancer (CRC) screening traditionally begins at age 50 years in people at average risk for the disease, those at high risk usually begin undergoing colonoscopies at an earlier age. Patients with cystic fibrosis fall under the latter category, wrote Andrea Gini, of the department of public health at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues, with an incidence of CRC up to 30 times higher than the general population, but their shorter lifespan has led to a “different trade-off between the benefits and harms of CRC screening.”

Between 2000 and 2015, the median predicted survival age for patients with cystic fibrosis increased from 33.3 years to 41.7 years; this increased survival has brought increased risk for other diseases, particularly in the GI tract, Mr. Gini and colleagues wrote in Gastroenterology. By using the Microsimulation Screening Analysis–Colon model – a joint project between Erasmus Medical Center and Memorial Sloan Kettering Cancer Center in New York – the investigators assessed the cost-effectiveness of CRC screening in patients with cystic fibrosis.

Three cohorts of 10 million patients each were simulated, with one cohort having undergone transplant, one cohort not having transplant, and one cohort of individuals without cystic fibrosis. The simulated patient age was 30 years in 2017. A total of 76 different colonoscopy-screening strategies were assessed, with each differing in screening interval (3, 5, or 10 years for colonoscopy), age to start screening (30, 35, 40, 45, or 50 years), and age to end screening (55, 60, 65, 70, or 75 years). The optimal screening strategy was determined based on a willingness-to-pay threshold of $100,000 per life-year gained, the investigators wrote.

In the absence of screening, the mortality rate for nontransplant cystic fibrosis patients was 19.1 per 1,000 people, and the rate for cystic fibrosis patients who had undergone transplant was 22.3 per 1,000 people. The standard screening strategy prevented more than 73% of CRC deaths in the general population, 66% of deaths in nontransplant cystic fibrosis patients, and 36% of deaths in cystic fibrosis patients with transplant; however, the model predicted that only 22% of individuals who received a transplant and 36% of those who did not would reach the age of 50 years.

According to the model, the optimal colonoscopy-screening strategy for nontransplant patients was one screen every 5 years, starting at 40 and screening until the age of 75. The incremental cost-effectiveness ratio (ICER) was $84,000 per life-year gained; CRC incidence was reduced by 52% and CRC mortality was reduced by 79%. For transplant patients, the best strategy was one screen every 3 years between the ages of 35 and 55, which reduced CRC mortality by 82% at an ICER of $71,000 per life-year gained.

In a separate analysis of fecal immunochemical testing, a less-demanding alternative to colonoscopy, the optimal screening strategy was an annual test between the age of 35 and 75 years for nontransplant cystic fibrosis patients, for an ICER of $47,000 per life-year gained and a CRC mortality reduction of 78%. The best strategy for transplant patients was once a year between the ages of 30 and 60, which reduced CRC mortality by 77% at an ICER of $86,000 per life-year gained. While fecal immunochemical testing may be more cost effective than colonoscopy, “specific evidence of its performance in the cystic fibrosis population is required before considering this screening modality,” the investigators noted.

“This study indicates that there is benefit to earlier CRC screening in the cystic fibrosis population and [that it] can be done at acceptable costs,” the investigators wrote. “The findings of this analysis support clinicians, researchers, and policy makers who aim to define a tailored CRC screening for individuals with cystic fibrosis in the United States.”

The study was funded by the Cystic Fibrosis Foundation, the Cancer Intervention and Surveillance Modeling Network consortium, and Memorial Sloan Kettering Cancer Center. The investigators reported no conflicts of interest.

Help your patients understand what do expect during and how to prepare for a colonoscopy by sharing AGA’s patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/colonoscopy.

[email protected]

SOURCE: Gini A et al. Gastroenterology. 2017 Dec 27. doi: 10.1053/j.gastro.2017.12.011.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.

Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.

The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”

To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.

“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”

Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.

The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.

For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.

Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.

The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”

To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.

“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”

Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.

The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.

For most patients taking antiplatelet and/or anticoagulant therapies, the proton pump inhibitor (PPI) pantoprazole is unnecessary, based on findings from the prospective COMPASS trial, which involved more than 17,000 participants.

Pantoprazole may reduce the risk of bleeding from gastroduodenal lesions, but it is unlikely to prevent upper-gastrointestinal events, reported lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Canada, and colleagues.

The investigators wrote in Gastroenterology, “Guidelines suggest that patients receiving the combination of antiplatelet and anticoagulant therapy should receive PPIs to reduce the risk of upper-GI bleeding. However … there are no randomized data to support the use of PPI therapy in patients taking oral anticoagulants, and a paucity of data relating to aspirin.”

To fill this knowledge gap, the investigators recruited 17,598 participants from 33 countries who had stable peripheral artery disease and cardiovascular disease. Participants were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or a combination of 2.5-mg rivaroxaban twice daily with 100-mg aspirin once daily. This part of the trial was discontinued before completion because of early cardiovascular advantages associated with combination therapy over aspirin alone, and related findings were reported previously. While combination therapy did reduce cardiovascular risks, it had less favorable effects on gut health, highlighted by an associated increase in major GI bleeding events. Despite early cessation of the cardiovascular portion of the trial, the pantoprazole regimen was continued, offering a look at the effect of long-term PPI use on gut health.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. The primary efficacy outcome was time to first upper-GI clinical event, defined as a composite of the following: upper-GI obstruction, perforation, at least five gastroduodenal erosions with at least 3 days of GI pain, symptomatic gastroduodenal ulcer involving at least 3 days of GI pain, overt upper-GI bleeding of unknown origin, occult bleeding (drop in hemoglobin of at least 2 g/dL), overt bleeding with a gastroduodenal lesion (active bleeding during endoscopy), or a symptomatic gastroduodenal ulcer involving at least 3 days of GI pain. In addition to this measure, the investigators evaluated a post-hoc endpoint with a looser definition of peptic ulcer events, most notably eliminating the requirement that a lesion be actively bleeding during endoscopy.

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking a nonsteroidal anti-inflammatory drug (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group, after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis showed that upper-GI events occurred marginally less often in the pantoprazole group than the placebo group, but without statistical significance (1.2% vs. 1.3%; P = .35). Of the outcomes measured, only overt bleeding of gastroduodenal origin detected by radiography or endoscopy was statistically less common in the pantoprazole group than the placebo group, with a 48% reduced rate (0.2% vs. 0.4%; P = .03). No statistical efficacy differences or statistical interactions were detected between population subgroups.

“The data suggest that routine use of PPI therapy is not warranted for patients receiving low-dose rivaroxaban with or without aspirin for the prevention of atherothrombotic events in patients with stable coronary artery disease or symptomatic peripheral artery disease, as there was no overall impact on clinical upper-GI events or upper-GI bleeding,” the investigators wrote. “This is in contrast to previous systematic reviews of randomized trials reporting that PPIs were associated with a 50%-70% reduction in bleeding and symptomatic peptic ulcers related to nonsteroidal anti-inflammatory drugs, including in the critical care setting.”

Post-hoc analysis, which allowed for a broader definition of upper-GI events related to gastroduodenal ulcers, revealed a slightly greater reduction in risk of bleeding lesions in patients taking pantoprazole, compared with placebo (hazard ratio, 0.45), and additional risk reductions for peptic ulcers (HR, 0.46) and erosions (HR, 0.33). Ultimately, pantoprazole reduced the combined rate of post-hoc events by 56%.

The investigators noted that these ulcer- and erosion-reducing effects of pantoprazole align with previous reports. “It is therefore possible that PPIs might be beneficial for patients at particularly high risk for peptic ulcer disease who are also taking aspirin and/or anticoagulants,” the investigators concluded.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 2. doi: 10.1053/j.gastro.2019.04.041.

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

A variety of demographic and disease-related factors contribute to poorer quality of life in patients with nonalcoholic fatty liver disease (NAFLD), based on questionnaires involving 304 European patients.

In contrast with previous research, lobular inflammation, but not hepatic fibrosis, was associated with worse quality of life, reported to lead author Yvonne Huber, MD, of Johannes Gutenberg University in Mainz, Germany, and colleagues. Women and those with advanced disease or comorbidities had the lowest health-related quality of life (HRQL) scores. The investigators suggested that these findings could be used for treatment planning at a population and patient level.

“With the emergence of medical therapy for [nonalcoholic steatohepatitis (NASH)], it will be of importance to identify patients with the highest unmet need for treatment,” the investigators wrote in Clinical Gastroenterology and Hepatology, emphasizing that therapies targeting inflammation could provide the greatest relief.

To determine which patients with NAFLD were most affected by their condition, the investigators used the Chronic Liver Disease Questionnaire (CLDQ), which assesses physical, mental, social, and emotional function, with lower scores indicating poorer health-related quality of life. “[The CLDQ] more specifically addresses symptoms of patients with chronic liver disease, including extrahepatic manifestations, compared with traditional HRQL measures such as the [Short Form–36 (SF-36)] Health Survey Questionnaire,” the investigators explained. Recent research has used the CLDQ to reveal a variety of findings, the investigators noted, such as a 2016 study by Alt and colleagues outlining the most common symptoms in noninfectious chronic liver disease (abdominal discomfort, fatigue, and anxiety), and two studies by Younossi and colleagues describing quality of life improvements after curing hepatitis C virus, and negative impacts of viremia and hepatic inflammation in patients with hepatitis B.

The current study involved 304 patients with histologically confirmed NAFLD who were prospectively entered into the European NAFLD registry via centers in Germany (n = 133), the United Kingdom (n = 154), and Spain (n = 17). Patient data included demographic factors, laboratory findings, and histologic features. Within 6 months of liver biopsy, patients completed the CLDQ.

The mean patient age was 52.3 years, with slightly more men than women (53.3% vs. 46.7%). Most patients (75%) were obese, leading to a median body mass index of 33.3 kg/m². More than two-thirds of patients (69.1%) had NASH, while approximately half of the population (51.4%) had moderate steatosis, no or low-grade fibrosis (F0-2, 58.2%), and no or low-grade lobular inflammation (grade 0 or 1, 54.7%). The three countries had significantly different population profiles; for example, the United Kingdom had an approximately 10% higher prevalence of type 2 diabetes and obesity compared with the entire cohort, but a decreased arterial hypertension rate of a similar magnitude. The United Kingdom also had a significantly lower mean CLDQ score than that of the study population as a whole (4.73 vs. 4.99).

Analysis of the entire cohort revealed that a variety of demographic and disease-related factors negatively impacted health-related quality of life. Women had a significantly lower mean CLDQ score than that of men (5.31 vs. 4.62; P less than .001), more often reporting abdominal symptoms, fatigue, systemic symptoms, reduced activity, diminished emotional functioning, and worry. CLDQ overall score was negatively influenced by obesity (4.83 vs. 5.46), type 2 diabetes (4.74 vs. 5.25), and hyperlipidemia (4.84 vs. 5.24), but not hypertension. Laboratory findings that negatively correlated with CLDQ included aspartate transaminase (AST) and HbA_1c, whereas ferritin was positively correlated.

Generally, patients with NASH reported worse quality of life than that of those with just NAFLD (4.85 vs. 5.31). Factors contributing most to this disparity were fatigue, systemic symptoms, activity, and worry. On a histologic level, hepatic steatosis, ballooning, and lobular inflammation predicted poorer quality of life; although advanced fibrosis and compensated cirrhosis were associated with a trend toward reduced quality of life, this pattern lacked statistical significance. Multivariate analysis, which accounted for age, sex, body mass index, country, and type 2 diabetes, revealed independent associations between reduced quality of life and type 2 diabetes, sex, age, body mass index, and hepatic inflammation, but not fibrosis.

“The striking finding of the current analysis in this well-characterized European cohort was that, in contrast to the published data on predictors of overall and liver-specific mortality, lobular inflammation correlated independently with HRQL,” the investigators wrote. “These results differ from the NASH [Clinical Research Network] cohort, which found lower HRQL using the generic [SF-36 Health Survey Questionnaire] in NASH compared with a healthy U.S. population and a significant effect in cirrhosis only.” The investigators suggested that mechanistic differences in disease progression could explain this discordance.

Although hepatic fibrosis has been tied with quality of life by some studies, the investigators pointed out that patients with chronic hepatitis B or C have reported improved quality of life after viral elimination or suppression, which reduce inflammation, but not fibrosis. “On the basis of the current analysis, it can be expected that improvement of steatohepatitis, and in particular lobular inflammation, will have measurable influence on HRQL even independently of fibrosis improvement,” the investigators concluded.

The study was funded by H2020. The investigators reported no conflicts of interest.

SOURCE: Huber Y et al. CGH. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.016.

A variety of demographic and disease-related factors contribute to poorer quality of life in patients with nonalcoholic fatty liver disease (NAFLD), based on questionnaires involving 304 European patients.

In contrast with previous research, lobular inflammation, but not hepatic fibrosis, was associated with worse quality of life, reported to lead author Yvonne Huber, MD, of Johannes Gutenberg University in Mainz, Germany, and colleagues. Women and those with advanced disease or comorbidities had the lowest health-related quality of life (HRQL) scores. The investigators suggested that these findings could be used for treatment planning at a population and patient level.

“With the emergence of medical therapy for [nonalcoholic steatohepatitis (NASH)], it will be of importance to identify patients with the highest unmet need for treatment,” the investigators wrote in Clinical Gastroenterology and Hepatology, emphasizing that therapies targeting inflammation could provide the greatest relief.

To determine which patients with NAFLD were most affected by their condition, the investigators used the Chronic Liver Disease Questionnaire (CLDQ), which assesses physical, mental, social, and emotional function, with lower scores indicating poorer health-related quality of life. “[The CLDQ] more specifically addresses symptoms of patients with chronic liver disease, including extrahepatic manifestations, compared with traditional HRQL measures such as the [Short Form–36 (SF-36)] Health Survey Questionnaire,” the investigators explained. Recent research has used the CLDQ to reveal a variety of findings, the investigators noted, such as a 2016 study by Alt and colleagues outlining the most common symptoms in noninfectious chronic liver disease (abdominal discomfort, fatigue, and anxiety), and two studies by Younossi and colleagues describing quality of life improvements after curing hepatitis C virus, and negative impacts of viremia and hepatic inflammation in patients with hepatitis B.

The current study involved 304 patients with histologically confirmed NAFLD who were prospectively entered into the European NAFLD registry via centers in Germany (n = 133), the United Kingdom (n = 154), and Spain (n = 17). Patient data included demographic factors, laboratory findings, and histologic features. Within 6 months of liver biopsy, patients completed the CLDQ.

The mean patient age was 52.3 years, with slightly more men than women (53.3% vs. 46.7%). Most patients (75%) were obese, leading to a median body mass index of 33.3 kg/m². More than two-thirds of patients (69.1%) had NASH, while approximately half of the population (51.4%) had moderate steatosis, no or low-grade fibrosis (F0-2, 58.2%), and no or low-grade lobular inflammation (grade 0 or 1, 54.7%). The three countries had significantly different population profiles; for example, the United Kingdom had an approximately 10% higher prevalence of type 2 diabetes and obesity compared with the entire cohort, but a decreased arterial hypertension rate of a similar magnitude. The United Kingdom also had a significantly lower mean CLDQ score than that of the study population as a whole (4.73 vs. 4.99).

Analysis of the entire cohort revealed that a variety of demographic and disease-related factors negatively impacted health-related quality of life. Women had a significantly lower mean CLDQ score than that of men (5.31 vs. 4.62; P less than .001), more often reporting abdominal symptoms, fatigue, systemic symptoms, reduced activity, diminished emotional functioning, and worry. CLDQ overall score was negatively influenced by obesity (4.83 vs. 5.46), type 2 diabetes (4.74 vs. 5.25), and hyperlipidemia (4.84 vs. 5.24), but not hypertension. Laboratory findings that negatively correlated with CLDQ included aspartate transaminase (AST) and HbA_1c, whereas ferritin was positively correlated.

Generally, patients with NASH reported worse quality of life than that of those with just NAFLD (4.85 vs. 5.31). Factors contributing most to this disparity were fatigue, systemic symptoms, activity, and worry. On a histologic level, hepatic steatosis, ballooning, and lobular inflammation predicted poorer quality of life; although advanced fibrosis and compensated cirrhosis were associated with a trend toward reduced quality of life, this pattern lacked statistical significance. Multivariate analysis, which accounted for age, sex, body mass index, country, and type 2 diabetes, revealed independent associations between reduced quality of life and type 2 diabetes, sex, age, body mass index, and hepatic inflammation, but not fibrosis.

“The striking finding of the current analysis in this well-characterized European cohort was that, in contrast to the published data on predictors of overall and liver-specific mortality, lobular inflammation correlated independently with HRQL,” the investigators wrote. “These results differ from the NASH [Clinical Research Network] cohort, which found lower HRQL using the generic [SF-36 Health Survey Questionnaire] in NASH compared with a healthy U.S. population and a significant effect in cirrhosis only.” The investigators suggested that mechanistic differences in disease progression could explain this discordance.

Although hepatic fibrosis has been tied with quality of life by some studies, the investigators pointed out that patients with chronic hepatitis B or C have reported improved quality of life after viral elimination or suppression, which reduce inflammation, but not fibrosis. “On the basis of the current analysis, it can be expected that improvement of steatohepatitis, and in particular lobular inflammation, will have measurable influence on HRQL even independently of fibrosis improvement,” the investigators concluded.

The study was funded by H2020. The investigators reported no conflicts of interest.

SOURCE: Huber Y et al. CGH. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.016.

A variety of demographic and disease-related factors contribute to poorer quality of life in patients with nonalcoholic fatty liver disease (NAFLD), based on questionnaires involving 304 European patients.

In contrast with previous research, lobular inflammation, but not hepatic fibrosis, was associated with worse quality of life, reported to lead author Yvonne Huber, MD, of Johannes Gutenberg University in Mainz, Germany, and colleagues. Women and those with advanced disease or comorbidities had the lowest health-related quality of life (HRQL) scores. The investigators suggested that these findings could be used for treatment planning at a population and patient level.

“With the emergence of medical therapy for [nonalcoholic steatohepatitis (NASH)], it will be of importance to identify patients with the highest unmet need for treatment,” the investigators wrote in Clinical Gastroenterology and Hepatology, emphasizing that therapies targeting inflammation could provide the greatest relief.

To determine which patients with NAFLD were most affected by their condition, the investigators used the Chronic Liver Disease Questionnaire (CLDQ), which assesses physical, mental, social, and emotional function, with lower scores indicating poorer health-related quality of life. “[The CLDQ] more specifically addresses symptoms of patients with chronic liver disease, including extrahepatic manifestations, compared with traditional HRQL measures such as the [Short Form–36 (SF-36)] Health Survey Questionnaire,” the investigators explained. Recent research has used the CLDQ to reveal a variety of findings, the investigators noted, such as a 2016 study by Alt and colleagues outlining the most common symptoms in noninfectious chronic liver disease (abdominal discomfort, fatigue, and anxiety), and two studies by Younossi and colleagues describing quality of life improvements after curing hepatitis C virus, and negative impacts of viremia and hepatic inflammation in patients with hepatitis B.

The current study involved 304 patients with histologically confirmed NAFLD who were prospectively entered into the European NAFLD registry via centers in Germany (n = 133), the United Kingdom (n = 154), and Spain (n = 17). Patient data included demographic factors, laboratory findings, and histologic features. Within 6 months of liver biopsy, patients completed the CLDQ.

The mean patient age was 52.3 years, with slightly more men than women (53.3% vs. 46.7%). Most patients (75%) were obese, leading to a median body mass index of 33.3 kg/m². More than two-thirds of patients (69.1%) had NASH, while approximately half of the population (51.4%) had moderate steatosis, no or low-grade fibrosis (F0-2, 58.2%), and no or low-grade lobular inflammation (grade 0 or 1, 54.7%). The three countries had significantly different population profiles; for example, the United Kingdom had an approximately 10% higher prevalence of type 2 diabetes and obesity compared with the entire cohort, but a decreased arterial hypertension rate of a similar magnitude. The United Kingdom also had a significantly lower mean CLDQ score than that of the study population as a whole (4.73 vs. 4.99).

Analysis of the entire cohort revealed that a variety of demographic and disease-related factors negatively impacted health-related quality of life. Women had a significantly lower mean CLDQ score than that of men (5.31 vs. 4.62; P less than .001), more often reporting abdominal symptoms, fatigue, systemic symptoms, reduced activity, diminished emotional functioning, and worry. CLDQ overall score was negatively influenced by obesity (4.83 vs. 5.46), type 2 diabetes (4.74 vs. 5.25), and hyperlipidemia (4.84 vs. 5.24), but not hypertension. Laboratory findings that negatively correlated with CLDQ included aspartate transaminase (AST) and HbA_1c, whereas ferritin was positively correlated.

Generally, patients with NASH reported worse quality of life than that of those with just NAFLD (4.85 vs. 5.31). Factors contributing most to this disparity were fatigue, systemic symptoms, activity, and worry. On a histologic level, hepatic steatosis, ballooning, and lobular inflammation predicted poorer quality of life; although advanced fibrosis and compensated cirrhosis were associated with a trend toward reduced quality of life, this pattern lacked statistical significance. Multivariate analysis, which accounted for age, sex, body mass index, country, and type 2 diabetes, revealed independent associations between reduced quality of life and type 2 diabetes, sex, age, body mass index, and hepatic inflammation, but not fibrosis.

“The striking finding of the current analysis in this well-characterized European cohort was that, in contrast to the published data on predictors of overall and liver-specific mortality, lobular inflammation correlated independently with HRQL,” the investigators wrote. “These results differ from the NASH [Clinical Research Network] cohort, which found lower HRQL using the generic [SF-36 Health Survey Questionnaire] in NASH compared with a healthy U.S. population and a significant effect in cirrhosis only.” The investigators suggested that mechanistic differences in disease progression could explain this discordance.

Although hepatic fibrosis has been tied with quality of life by some studies, the investigators pointed out that patients with chronic hepatitis B or C have reported improved quality of life after viral elimination or suppression, which reduce inflammation, but not fibrosis. “On the basis of the current analysis, it can be expected that improvement of steatohepatitis, and in particular lobular inflammation, will have measurable influence on HRQL even independently of fibrosis improvement,” the investigators concluded.

The study was funded by H2020. The investigators reported no conflicts of interest.

SOURCE: Huber Y et al. CGH. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.016.