DDW 2017

 

The final session of the course opened with Uri Ladabaum, MD, entertaining the question “Colon cancer screening and surveillance: who, when, and how?” Dr. Ladabaum pointed out that there is consensus that colorectal cancer screening for average-risk individuals should begin at age 50 with a choice of modalities and that surveillance depends on the findings on each colonoscopy. He reviewed the evidence for screening modalities and for surveillance and offered perspectives on the role of the gastroenterologist/colonoscopist in the quality of colonsocopy. Douglas K. Rex, MD, AGAF followed by asking “Does every big polyp need EMR?” Dr. Rex discussed the available approaches to the large colonic polyp, including endoscopic mucosal resection, endoscopic submucosal dissection, and surgery. He provided evidence for the advantages and expanded use of EMR, with the conclusion that almost every large benign polyp needs EMR.

Asyia Ahmad, MD followed with a talk entitled, “When in Rome: Update on the Rome IV criteria for functional bowel disorders.” Dr. Ahmed explained that the 2016 Rome IV classification of functional GI disorders describes a spectrum of disorders instead of the distinct ones in Rome III. Additionally, the importance of culture and language is now taken into account, with descriptions of symptoms that occur in these contexts. Novel areas of research and concepts comprise biopsychosocial, clinical applications, the patient-physician relationship, and therapies aimed at brain-gut interactions. Such therapies include cognitive-behavioral therapy, hypnosis, relaxation techniques, psychodynamic therapy, biofeedback, and mindfulness.

Jennifer A. Christie, MD, then spoke on “Pelvic floor dysfunction and constipation.” Dr. Christie stressed the importance of a good history and the digital rectal exam in diagnosis of pelvic floor dysfunction. When over-the-counter or prescribed medications are not effective, the work-up should include anorectal manometry, balloon expulsion, and colonic transit testing. Attempts should be made to remove all potential offending agents, such as anticholinergics, narcotics, calcium channel blockers, and beta-blockers. Biofeedback is a safe and effective treatment for pelvic floor dysfunction. Lin Chang, MD, AGAF, continued with a talk on irritable bowel syndrome, which can be considered a combination of disorders, with clusters of symptoms and subgroups. There must be recurrent abdominal pain or discomfort at least 1 day/week for the prior 3 months, associated with 2 or more of the following: a relationship to defecation, change in stool frequency, or stool form/appearance. Risk includes genetic and environmental factors, stress/abuse, and acute gastroenteritis. After a structured evaluation, a graded treatment response is undertaken, ranging from diet/lifestyle counseling to pharmacotherapy to psychological therapies.

Neil Hyman, MD, concluded the session with a talk entitled “Disorders of the anorectum,” also stressing that the history is key to the diagnosis, with an emphasis on asking the right questions. Pain may be related to fissures, thrombosed hemorrhoids, abscesses, and proctalgia/levator spasm. New technologies, and pharmacological and surgical approaches were discussed.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Cohen is the chief of the division of gastroenterology and hepatology in the Weill department of medicine, New York–Presbyterian Hospital Center, New York.

 

The final session of the course opened with Uri Ladabaum, MD, entertaining the question “Colon cancer screening and surveillance: who, when, and how?” Dr. Ladabaum pointed out that there is consensus that colorectal cancer screening for average-risk individuals should begin at age 50 with a choice of modalities and that surveillance depends on the findings on each colonoscopy. He reviewed the evidence for screening modalities and for surveillance and offered perspectives on the role of the gastroenterologist/colonoscopist in the quality of colonsocopy. Douglas K. Rex, MD, AGAF followed by asking “Does every big polyp need EMR?” Dr. Rex discussed the available approaches to the large colonic polyp, including endoscopic mucosal resection, endoscopic submucosal dissection, and surgery. He provided evidence for the advantages and expanded use of EMR, with the conclusion that almost every large benign polyp needs EMR.

Asyia Ahmad, MD followed with a talk entitled, “When in Rome: Update on the Rome IV criteria for functional bowel disorders.” Dr. Ahmed explained that the 2016 Rome IV classification of functional GI disorders describes a spectrum of disorders instead of the distinct ones in Rome III. Additionally, the importance of culture and language is now taken into account, with descriptions of symptoms that occur in these contexts. Novel areas of research and concepts comprise biopsychosocial, clinical applications, the patient-physician relationship, and therapies aimed at brain-gut interactions. Such therapies include cognitive-behavioral therapy, hypnosis, relaxation techniques, psychodynamic therapy, biofeedback, and mindfulness.

Jennifer A. Christie, MD, then spoke on “Pelvic floor dysfunction and constipation.” Dr. Christie stressed the importance of a good history and the digital rectal exam in diagnosis of pelvic floor dysfunction. When over-the-counter or prescribed medications are not effective, the work-up should include anorectal manometry, balloon expulsion, and colonic transit testing. Attempts should be made to remove all potential offending agents, such as anticholinergics, narcotics, calcium channel blockers, and beta-blockers. Biofeedback is a safe and effective treatment for pelvic floor dysfunction. Lin Chang, MD, AGAF, continued with a talk on irritable bowel syndrome, which can be considered a combination of disorders, with clusters of symptoms and subgroups. There must be recurrent abdominal pain or discomfort at least 1 day/week for the prior 3 months, associated with 2 or more of the following: a relationship to defecation, change in stool frequency, or stool form/appearance. Risk includes genetic and environmental factors, stress/abuse, and acute gastroenteritis. After a structured evaluation, a graded treatment response is undertaken, ranging from diet/lifestyle counseling to pharmacotherapy to psychological therapies.

Neil Hyman, MD, concluded the session with a talk entitled “Disorders of the anorectum,” also stressing that the history is key to the diagnosis, with an emphasis on asking the right questions. Pain may be related to fissures, thrombosed hemorrhoids, abscesses, and proctalgia/levator spasm. New technologies, and pharmacological and surgical approaches were discussed.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Cohen is the chief of the division of gastroenterology and hepatology in the Weill department of medicine, New York–Presbyterian Hospital Center, New York.

 

The final session of the course opened with Uri Ladabaum, MD, entertaining the question “Colon cancer screening and surveillance: who, when, and how?” Dr. Ladabaum pointed out that there is consensus that colorectal cancer screening for average-risk individuals should begin at age 50 with a choice of modalities and that surveillance depends on the findings on each colonoscopy. He reviewed the evidence for screening modalities and for surveillance and offered perspectives on the role of the gastroenterologist/colonoscopist in the quality of colonsocopy. Douglas K. Rex, MD, AGAF followed by asking “Does every big polyp need EMR?” Dr. Rex discussed the available approaches to the large colonic polyp, including endoscopic mucosal resection, endoscopic submucosal dissection, and surgery. He provided evidence for the advantages and expanded use of EMR, with the conclusion that almost every large benign polyp needs EMR.

Asyia Ahmad, MD followed with a talk entitled, “When in Rome: Update on the Rome IV criteria for functional bowel disorders.” Dr. Ahmed explained that the 2016 Rome IV classification of functional GI disorders describes a spectrum of disorders instead of the distinct ones in Rome III. Additionally, the importance of culture and language is now taken into account, with descriptions of symptoms that occur in these contexts. Novel areas of research and concepts comprise biopsychosocial, clinical applications, the patient-physician relationship, and therapies aimed at brain-gut interactions. Such therapies include cognitive-behavioral therapy, hypnosis, relaxation techniques, psychodynamic therapy, biofeedback, and mindfulness.

Jennifer A. Christie, MD, then spoke on “Pelvic floor dysfunction and constipation.” Dr. Christie stressed the importance of a good history and the digital rectal exam in diagnosis of pelvic floor dysfunction. When over-the-counter or prescribed medications are not effective, the work-up should include anorectal manometry, balloon expulsion, and colonic transit testing. Attempts should be made to remove all potential offending agents, such as anticholinergics, narcotics, calcium channel blockers, and beta-blockers. Biofeedback is a safe and effective treatment for pelvic floor dysfunction. Lin Chang, MD, AGAF, continued with a talk on irritable bowel syndrome, which can be considered a combination of disorders, with clusters of symptoms and subgroups. There must be recurrent abdominal pain or discomfort at least 1 day/week for the prior 3 months, associated with 2 or more of the following: a relationship to defecation, change in stool frequency, or stool form/appearance. Risk includes genetic and environmental factors, stress/abuse, and acute gastroenteritis. After a structured evaluation, a graded treatment response is undertaken, ranging from diet/lifestyle counseling to pharmacotherapy to psychological therapies.

Neil Hyman, MD, concluded the session with a talk entitled “Disorders of the anorectum,” also stressing that the history is key to the diagnosis, with an emphasis on asking the right questions. Pain may be related to fissures, thrombosed hemorrhoids, abscesses, and proctalgia/levator spasm. New technologies, and pharmacological and surgical approaches were discussed.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Cohen is the chief of the division of gastroenterology and hepatology in the Weill department of medicine, New York–Presbyterian Hospital Center, New York.

 

Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.

David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.

William Sandborn, MD, AGAF, discussed “Severe ulcerative colitis in the hospitalized patient.” Severe UC is characterized by at least six bowel movements daily, blood in the stool, fever, tachycardia, anemia, and elevated ESR. Other predictors of severity include colonic dilation, deep ulcers, and lack of response to 3 days of IV corticosteroids (e.g., stool frequency more than 8/day or CRP more than 45 mg/L). About 70% of patients will respond to IV steroids; for those who don’t, options include IV cyclosporine or IV infliximab. These drugs are equivalent in efficacy; however, cyclosporine toxicity can include serious or fatal infections in up to 3% of patients. The challenge with infliximab is pharmacokinetics – many severely ill patients will have protein-losing colopathy, detectable fecal infliximab levels, and lower serum levels resulting in lack of response – so early dose escalation may be required. A day-by-day algorithm for managing severe UC in the hospital was reviewed (see Clin Gastroenterol Hepatol. 2012;10:1315-25).

Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.

Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.

 

Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.

David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.

William Sandborn, MD, AGAF, discussed “Severe ulcerative colitis in the hospitalized patient.” Severe UC is characterized by at least six bowel movements daily, blood in the stool, fever, tachycardia, anemia, and elevated ESR. Other predictors of severity include colonic dilation, deep ulcers, and lack of response to 3 days of IV corticosteroids (e.g., stool frequency more than 8/day or CRP more than 45 mg/L). About 70% of patients will respond to IV steroids; for those who don’t, options include IV cyclosporine or IV infliximab. These drugs are equivalent in efficacy; however, cyclosporine toxicity can include serious or fatal infections in up to 3% of patients. The challenge with infliximab is pharmacokinetics – many severely ill patients will have protein-losing colopathy, detectable fecal infliximab levels, and lower serum levels resulting in lack of response – so early dose escalation may be required. A day-by-day algorithm for managing severe UC in the hospital was reviewed (see Clin Gastroenterol Hepatol. 2012;10:1315-25).

Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.

Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.

 

Uma Mahadevan, MD, AGAF, and I moderated this session on IBD, and we were fortunate enough to secure four of the best IBD educators in the AGA.

David Rubin, MD, AGAF, opened with “Selecting the correct therapy for your outpatients with IBD: From mesalamine to biologics.” Treatment goals have evolved from symptom control to remission based on measures of inflammation (e.g., serum C-reactive protein, fecal calprotectin, or endoscopy). For ulcerative colitis (UC), high-risk markers include extensive disease, deep ulcers, younger age at diagnosis, elevated biomarkers, and early need for steroids or hospitalization. For Crohn’s disease (CD), these include younger age, extensive involvement, and fistulizing disease. The 5-aminosalicylate drugs remain a backbone in mild to moderate UC. Judicious use of corticosteroids is reasonable, but we need an exit strategy. The thiopurines are decent drugs, but studies have called into question their efficacy as monotherapy, and safety issues persist. Methotrexate is underutilized. The anti–tumor necrosis factor (TNF) biologics are excellent therapies but controversies persist as to whether these drugs require combination therapy or if they can be managed as “optimized monotherapy” with therapeutic drug monitoring (TDM). There are now two infliximab biosimilars available in the U.S.. Vedolizumab is an efficacious gut-selective anti-integrin (for both CD and UC). Ustekinumab, an anti-IL-12/23 antibody, is now available for moderate to severe CD, and has a favorable safety profile.

William Sandborn, MD, AGAF, discussed “Severe ulcerative colitis in the hospitalized patient.” Severe UC is characterized by at least six bowel movements daily, blood in the stool, fever, tachycardia, anemia, and elevated ESR. Other predictors of severity include colonic dilation, deep ulcers, and lack of response to 3 days of IV corticosteroids (e.g., stool frequency more than 8/day or CRP more than 45 mg/L). About 70% of patients will respond to IV steroids; for those who don’t, options include IV cyclosporine or IV infliximab. These drugs are equivalent in efficacy; however, cyclosporine toxicity can include serious or fatal infections in up to 3% of patients. The challenge with infliximab is pharmacokinetics – many severely ill patients will have protein-losing colopathy, detectable fecal infliximab levels, and lower serum levels resulting in lack of response – so early dose escalation may be required. A day-by-day algorithm for managing severe UC in the hospital was reviewed (see Clin Gastroenterol Hepatol. 2012;10:1315-25).

Fernando Velayos, MD, AGAF, discussed “Surveillance for dysplasia: What is the standard of care in 2017?” General principles for surveillance colonoscopy in IBD include having quiescent disease, since inflammation can reduce ability to detect lesions, and good colonic preparation. The three U.S. society guidelines recommend starting surveillance after 8 years of disease. Patients with concomitant primary schlerosing cholangitis should begin surveillance immediately. Frequency of surveillance ranges every 1-3 years depending on histology. A meta-analysis showed a higher incremental dysplasia yield with chromoendoscopy compared to standard white-light colonoscopy. If visible dysplasia can be endoscopically resected, then continued surveillance rather than colectomy is recommended.

Sunanda Kane, MD, AGAF, discussed “Managing special populations: the transitioning adolescent, the gravid, and the elderly.” The transition from pediatric to adult IBD care is a high-risk time because the patient may be lost to follow-up or not adhere to the medical regimen, resulting in increased risk of flare. Successful transition requires developmental maturity of the patient, a certain style of parental involvement, and care coordination of the medical team. For women with IBD considering pregnancy, active IBD at the time of conception significantly increases the risk of flare. Women with CD who have no history of perianal disease don’t have an increased risk of perianal disease with vaginal delivery. A meta-analysis of the risk of congenital malformations with thiopurines found no significant association. Infliximab levels were likely to rise in the mother during the second and third trimesters (versus no increase with adalimumab), so one could consider TDM to guide dosing. In the PIANO study, anti-TNF therapy in the third trimester was neither associated with adverse pregnancy outcomes nor with infections up to 1 year for children. Patients who develop IBD later in life are more likely to have colonic inflammation. Elderly UC patients are more likely to require surgery, and postop mortality is higher for both CD and UC.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017. Dr. Loftus is a professor of medicine, division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn.

 

The session titled “The biliary tree and pancreas” provided an overview of the most important pancreaticobiliary diseases, allowing experts to delineate their approaches to challenging aspects of these conditions.

Timothy Gardner, MD, MS, focused on the management and treatment of sequelae in patients with acute pancreatitis. He provided support for the use of lactated Ringer’s as the fluid of choice, cautioning against over-resuscitation. He advised early oral feeds, without clear preference for nasogastric or nasojejunal administration. Dr. Gardner emphasized the importance of classifying type of fluid collection to optimize clinical decision making. Endoscopic techniques appear to be safer and as efficacious as surgical approaches. Regarding thrombosis, anticoagulation was recommended unless an absolute contraindication exists. He also recommended addressing symptomatic ductal disruptions.

Matthew J. DiMagno, MD, AGAF, provided important insights into chronic pancreatitis. He first advised classifying patients with recurrent attacks of pancreatitis. Also, pain patterns in chronic pancreatitis may be categorized into two groups: short, intermittent pain (type A) and constant pain (type B). The former can often be managed without invasive procedures, while the latter is often managed with interventions. When addressing the pain of chronic pancreatitis, clinicians need to establish the diagnosis, advise abstinence from alcohol and smoking, and advocate adequate nutrition and other treatments. The approach to constant pain requires exclusion of anatomic pathology and appropriate treatment of neuropathic and centralized pain. Assessment of duct morphology also impacts treatments; patients with dilated or large duct disease should undergo drainage procedures.

Douglas Adler, MD, AGAF, provided pointers on distinguishing between malignant and benign biliary strictures. Ruling out a malignant stricture entails use of multiple diagnostic modalities to image and to sample abnormalities, such as a dominant stricture in primary sclerosing cholangitis. Fluorescence in situ hybridization (FISH) and cholangioscopy are fairly widely used, while other techniques such as confocal laser endomicroscopy are used less frequently. Benign biliary strictures occur frequently in the liver transplant population, both anastomotic and nonanastomotic. Benign biliary strictures may also occur in chronic pancreatitis; importantly, these may mimic pancreatic cancer.

During my presentation, we focused on several aspects of pancreaticobiliary neoplasia. We reviewed the multiple genetic syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, and Lynch syndrome, all of which confer increased risk for pancreatic cancer. Endoscopic ultrasound guidance and adjunctive techniques (e.g., elastography) may improve imaging in the pancreas and improve targeting of biopsies. Needle-based confocal laser endomicroscopy is also available to provide real time cellular data, improving our ability to accurately diagnose and differentiate pancreatic cystic neoplasms. Endoscopic ultrasound–guided needle injection and other therapeutic techniques allow endoscopists to intervene therapeutically. Accurate management of pancreatic cysts depends largely on the accurate identification of mucinous cystic neoplasms. Recent guidelines delineate high-risk stigmata and worrisome features of branch-duct intraductal papillary mucinous neoplasm. We also reviewed less common neoplasms such as pancreatic neuroendocrine tumors and biliary neoplasms.
 

Dr. Kim is an assistant professor of gastroenterology at Mount Sinai Hospital, acting director of endoscopy, and director of endoscopic ultrasound at Mount Sinai Hospital, New York. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

The session titled “The biliary tree and pancreas” provided an overview of the most important pancreaticobiliary diseases, allowing experts to delineate their approaches to challenging aspects of these conditions.

Timothy Gardner, MD, MS, focused on the management and treatment of sequelae in patients with acute pancreatitis. He provided support for the use of lactated Ringer’s as the fluid of choice, cautioning against over-resuscitation. He advised early oral feeds, without clear preference for nasogastric or nasojejunal administration. Dr. Gardner emphasized the importance of classifying type of fluid collection to optimize clinical decision making. Endoscopic techniques appear to be safer and as efficacious as surgical approaches. Regarding thrombosis, anticoagulation was recommended unless an absolute contraindication exists. He also recommended addressing symptomatic ductal disruptions.

Matthew J. DiMagno, MD, AGAF, provided important insights into chronic pancreatitis. He first advised classifying patients with recurrent attacks of pancreatitis. Also, pain patterns in chronic pancreatitis may be categorized into two groups: short, intermittent pain (type A) and constant pain (type B). The former can often be managed without invasive procedures, while the latter is often managed with interventions. When addressing the pain of chronic pancreatitis, clinicians need to establish the diagnosis, advise abstinence from alcohol and smoking, and advocate adequate nutrition and other treatments. The approach to constant pain requires exclusion of anatomic pathology and appropriate treatment of neuropathic and centralized pain. Assessment of duct morphology also impacts treatments; patients with dilated or large duct disease should undergo drainage procedures.

Douglas Adler, MD, AGAF, provided pointers on distinguishing between malignant and benign biliary strictures. Ruling out a malignant stricture entails use of multiple diagnostic modalities to image and to sample abnormalities, such as a dominant stricture in primary sclerosing cholangitis. Fluorescence in situ hybridization (FISH) and cholangioscopy are fairly widely used, while other techniques such as confocal laser endomicroscopy are used less frequently. Benign biliary strictures occur frequently in the liver transplant population, both anastomotic and nonanastomotic. Benign biliary strictures may also occur in chronic pancreatitis; importantly, these may mimic pancreatic cancer.

During my presentation, we focused on several aspects of pancreaticobiliary neoplasia. We reviewed the multiple genetic syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, and Lynch syndrome, all of which confer increased risk for pancreatic cancer. Endoscopic ultrasound guidance and adjunctive techniques (e.g., elastography) may improve imaging in the pancreas and improve targeting of biopsies. Needle-based confocal laser endomicroscopy is also available to provide real time cellular data, improving our ability to accurately diagnose and differentiate pancreatic cystic neoplasms. Endoscopic ultrasound–guided needle injection and other therapeutic techniques allow endoscopists to intervene therapeutically. Accurate management of pancreatic cysts depends largely on the accurate identification of mucinous cystic neoplasms. Recent guidelines delineate high-risk stigmata and worrisome features of branch-duct intraductal papillary mucinous neoplasm. We also reviewed less common neoplasms such as pancreatic neuroendocrine tumors and biliary neoplasms.
 

Dr. Kim is an assistant professor of gastroenterology at Mount Sinai Hospital, acting director of endoscopy, and director of endoscopic ultrasound at Mount Sinai Hospital, New York. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

The session titled “The biliary tree and pancreas” provided an overview of the most important pancreaticobiliary diseases, allowing experts to delineate their approaches to challenging aspects of these conditions.

Timothy Gardner, MD, MS, focused on the management and treatment of sequelae in patients with acute pancreatitis. He provided support for the use of lactated Ringer’s as the fluid of choice, cautioning against over-resuscitation. He advised early oral feeds, without clear preference for nasogastric or nasojejunal administration. Dr. Gardner emphasized the importance of classifying type of fluid collection to optimize clinical decision making. Endoscopic techniques appear to be safer and as efficacious as surgical approaches. Regarding thrombosis, anticoagulation was recommended unless an absolute contraindication exists. He also recommended addressing symptomatic ductal disruptions.

Matthew J. DiMagno, MD, AGAF, provided important insights into chronic pancreatitis. He first advised classifying patients with recurrent attacks of pancreatitis. Also, pain patterns in chronic pancreatitis may be categorized into two groups: short, intermittent pain (type A) and constant pain (type B). The former can often be managed without invasive procedures, while the latter is often managed with interventions. When addressing the pain of chronic pancreatitis, clinicians need to establish the diagnosis, advise abstinence from alcohol and smoking, and advocate adequate nutrition and other treatments. The approach to constant pain requires exclusion of anatomic pathology and appropriate treatment of neuropathic and centralized pain. Assessment of duct morphology also impacts treatments; patients with dilated or large duct disease should undergo drainage procedures.

Douglas Adler, MD, AGAF, provided pointers on distinguishing between malignant and benign biliary strictures. Ruling out a malignant stricture entails use of multiple diagnostic modalities to image and to sample abnormalities, such as a dominant stricture in primary sclerosing cholangitis. Fluorescence in situ hybridization (FISH) and cholangioscopy are fairly widely used, while other techniques such as confocal laser endomicroscopy are used less frequently. Benign biliary strictures occur frequently in the liver transplant population, both anastomotic and nonanastomotic. Benign biliary strictures may also occur in chronic pancreatitis; importantly, these may mimic pancreatic cancer.

During my presentation, we focused on several aspects of pancreaticobiliary neoplasia. We reviewed the multiple genetic syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, and Lynch syndrome, all of which confer increased risk for pancreatic cancer. Endoscopic ultrasound guidance and adjunctive techniques (e.g., elastography) may improve imaging in the pancreas and improve targeting of biopsies. Needle-based confocal laser endomicroscopy is also available to provide real time cellular data, improving our ability to accurately diagnose and differentiate pancreatic cystic neoplasms. Endoscopic ultrasound–guided needle injection and other therapeutic techniques allow endoscopists to intervene therapeutically. Accurate management of pancreatic cysts depends largely on the accurate identification of mucinous cystic neoplasms. Recent guidelines delineate high-risk stigmata and worrisome features of branch-duct intraductal papillary mucinous neoplasm. We also reviewed less common neoplasms such as pancreatic neuroendocrine tumors and biliary neoplasms.
 

Dr. Kim is an assistant professor of gastroenterology at Mount Sinai Hospital, acting director of endoscopy, and director of endoscopic ultrasound at Mount Sinai Hospital, New York. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.

Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.

John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.

In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.

Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
 

 

Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.

Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.

John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.

In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.

Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
 

 

Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.

Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.

John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.

In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.

Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
 

 

Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.

From there, Octavia Pickett-Blakely MD, MHS, took us through the role of the microbiome in obesity (wouldn’t it be great to take probiotics or an annual fecal microbial transplant [FMT] to keep our weight under control?). She discussed the likely link between obesity and antibiotic use in early childhood and the different gut microbiota compositions in the obese and lean. Altered gut microbiota can affect energy homeostasis, which can then lead to obesity. She discussed the potential role of breastfeeding, low-fat, low-calorie, and high-fruit-vegetable-fiber diets on increasing microbial richness and reducing obesity. While diet and a sedentary lifestyle remain the primary drivers of obesity, host genetics, environment, and gut permeability all play a role.

Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.

We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
 

Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.

From there, Octavia Pickett-Blakely MD, MHS, took us through the role of the microbiome in obesity (wouldn’t it be great to take probiotics or an annual fecal microbial transplant [FMT] to keep our weight under control?). She discussed the likely link between obesity and antibiotic use in early childhood and the different gut microbiota compositions in the obese and lean. Altered gut microbiota can affect energy homeostasis, which can then lead to obesity. She discussed the potential role of breastfeeding, low-fat, low-calorie, and high-fruit-vegetable-fiber diets on increasing microbial richness and reducing obesity. While diet and a sedentary lifestyle remain the primary drivers of obesity, host genetics, environment, and gut permeability all play a role.

Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.

We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
 

Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

The 2017 Postgraduate Course started out with four hot topics that dominated the year – opioid dependence, a cure for hepatitis C, and understanding and then manipulating the microbiome. From David Dickerson, MD, we learned that abdominal pain is complex and with an evolving classification scheme. Ignoring the biopsychosocial aspects and origins of pain is a sure way to lead to addiction and “pain behavior.” He reviewed the opioid guidelines that involve a comprehensive approach to therapy – setting functional goals, assessing the risks and benefits, and using the lowest necessary doses of short-acting agents for a defined period of time and then reassessing. In patients with chronic pain and opioid dependence, the gastroenterologist should seek the help of a chronic pain specialist. We should also refer for nonpharmacologic therapy such as cognitive behavioral therapy and biofeedback.

From there, Octavia Pickett-Blakely MD, MHS, took us through the role of the microbiome in obesity (wouldn’t it be great to take probiotics or an annual fecal microbial transplant [FMT] to keep our weight under control?). She discussed the likely link between obesity and antibiotic use in early childhood and the different gut microbiota compositions in the obese and lean. Altered gut microbiota can affect energy homeostasis, which can then lead to obesity. She discussed the potential role of breastfeeding, low-fat, low-calorie, and high-fruit-vegetable-fiber diets on increasing microbial richness and reducing obesity. While diet and a sedentary lifestyle remain the primary drivers of obesity, host genetics, environment, and gut permeability all play a role.

Norah Terrault, MD, MPH, discussed management of chronic hepatitis C (HCV) after the cure, achievable in more than 95% of patients, which has resulted in a sharp decline in listings for liver transplant. A cure is defined as undetectable HCV RNA 12 weeks after completion of therapy. So what happens next? If the patient is at risk for reinfection, they should have HCV RNA testing annually or if their liver enzymes increase. Otherwise, if their pretreatment fibrosis is low stage, no further monitoring is needed and they can follow up with their primary care provider. Intermediate-stage fibrosis should be monitored for progression. Advanced-stage fibrosis needs long-term follow-up for hepatocellular carcinoma and variceal surveillance. Modifiable risk factors, i.e., metabolic fatty liver and alcohol abuse, should be identified with appropriate counseling provided.

We went back to the microbiome for our last talk: Larry Brandt, MD, AGAF, discussed FMT for Clostridium difficile infection (CDI). Patients should be considered for FMT if they have more than 3 recurrences of mild to moderate CDI and failure to respond to standard therapy; more than 2 episodes of CDI resulting in hospitalization and significant morbidity; moderate CDI with no response after 1 week of standard therapy; and severe CDI with no response to standard therapy within 48 hours. Serious adverse events associated with FMT include infections and perhaps new-onset immune-mediated disease such as Sjogren’s, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. It is hoped that the NIH-sponsored AGA national registry for FMT will help better define outcomes and adverse events over the next 10 years.
 

Dr. Mahadevan is professor of clinical medicine at UCSF Medical Center, San Francisco. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

What distinguished this year’s course offering was the overall approach and philosophy to utilize educational processes and educational theory resulting in an educational program that adhered to the AGA’s commitment to high-quality, evidence-based, and theory-driven programming.

As a first step in planning the course, we performed a needs assessment. By identifying what learners need to know, we endeavored to develop the ideal course. Our course directors, supported by the AGA staff, reviewed past course evaluations, and in particular, the comments related to suggestions for future programs. We also reviewed and discussed with experts the emerging trend topics and need-to-know areas in GI and hepatology. In doing so, an outline of topics was created, which was subsequently approved by AGA Institute’s Education and Training Committee.

The next step was to require that every learning activity identify its objectives, in behavioral terms, so that postcourse assessments could determine if the objectives were met. While all speakers were required to provide objectives for their specific talks, the following represent the overall objectives of the course on which the course curriculum was based.

Objectives

At the completion of this course the attendee will be able to:

1. Identify new strategies in the evaluation and management of GI and hepatobiliary problems

2. Recognize medical, surgical, and technological advances in the field of GI and hepatology

3. Apply new strategies for evaluation, therapeutic options, and technology to the optimal care of patients

It is challenging to craft large audience educational experiences so that they also address adult learning principles. We know that adult learners benefit from experiences that are relevant, are problem-centered (rather than content oriented), promote active learning, and provide feedback to the learner. We therefore requested that each session begin with a brief case. Having clinical examples helps learners frame the disease process, and can help demonstrate the importance of learning the material. Finally, all participants were given the opportunity to review each session, and the course in its entirety, to help us improve future programming.

Lunch sessions promoted active learning with the opportunity for interaction, and we also included case-based breakout sessions. Not only was CME accreditation provided, but Maintenance of Certification (MOC) credit was also available.

This educational offering provided a setting to hear from leaders in GI and hepatology, and for learners to gain new insights to take home and apply to the care of patients. The sections that follow provide brief summaries of the sessions from the course written by the moderators.

Please visit http://pgcourse.gastro.org/home to access the content from DDW.
 

Dr. Rose is a professor of medicine, the Senior Associate Dean for Education, University of Connecticut School of Medicine, Farmington, and the 2017 AGA Postgraduate Course Director. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

What distinguished this year’s course offering was the overall approach and philosophy to utilize educational processes and educational theory resulting in an educational program that adhered to the AGA’s commitment to high-quality, evidence-based, and theory-driven programming.

As a first step in planning the course, we performed a needs assessment. By identifying what learners need to know, we endeavored to develop the ideal course. Our course directors, supported by the AGA staff, reviewed past course evaluations, and in particular, the comments related to suggestions for future programs. We also reviewed and discussed with experts the emerging trend topics and need-to-know areas in GI and hepatology. In doing so, an outline of topics was created, which was subsequently approved by AGA Institute’s Education and Training Committee.

The next step was to require that every learning activity identify its objectives, in behavioral terms, so that postcourse assessments could determine if the objectives were met. While all speakers were required to provide objectives for their specific talks, the following represent the overall objectives of the course on which the course curriculum was based.

Objectives

At the completion of this course the attendee will be able to:

1. Identify new strategies in the evaluation and management of GI and hepatobiliary problems

2. Recognize medical, surgical, and technological advances in the field of GI and hepatology

3. Apply new strategies for evaluation, therapeutic options, and technology to the optimal care of patients

It is challenging to craft large audience educational experiences so that they also address adult learning principles. We know that adult learners benefit from experiences that are relevant, are problem-centered (rather than content oriented), promote active learning, and provide feedback to the learner. We therefore requested that each session begin with a brief case. Having clinical examples helps learners frame the disease process, and can help demonstrate the importance of learning the material. Finally, all participants were given the opportunity to review each session, and the course in its entirety, to help us improve future programming.

Lunch sessions promoted active learning with the opportunity for interaction, and we also included case-based breakout sessions. Not only was CME accreditation provided, but Maintenance of Certification (MOC) credit was also available.

This educational offering provided a setting to hear from leaders in GI and hepatology, and for learners to gain new insights to take home and apply to the care of patients. The sections that follow provide brief summaries of the sessions from the course written by the moderators.

Please visit http://pgcourse.gastro.org/home to access the content from DDW.
 

Dr. Rose is a professor of medicine, the Senior Associate Dean for Education, University of Connecticut School of Medicine, Farmington, and the 2017 AGA Postgraduate Course Director. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

What distinguished this year’s course offering was the overall approach and philosophy to utilize educational processes and educational theory resulting in an educational program that adhered to the AGA’s commitment to high-quality, evidence-based, and theory-driven programming.

As a first step in planning the course, we performed a needs assessment. By identifying what learners need to know, we endeavored to develop the ideal course. Our course directors, supported by the AGA staff, reviewed past course evaluations, and in particular, the comments related to suggestions for future programs. We also reviewed and discussed with experts the emerging trend topics and need-to-know areas in GI and hepatology. In doing so, an outline of topics was created, which was subsequently approved by AGA Institute’s Education and Training Committee.

The next step was to require that every learning activity identify its objectives, in behavioral terms, so that postcourse assessments could determine if the objectives were met. While all speakers were required to provide objectives for their specific talks, the following represent the overall objectives of the course on which the course curriculum was based.

Objectives

At the completion of this course the attendee will be able to:

1. Identify new strategies in the evaluation and management of GI and hepatobiliary problems

2. Recognize medical, surgical, and technological advances in the field of GI and hepatology

3. Apply new strategies for evaluation, therapeutic options, and technology to the optimal care of patients

It is challenging to craft large audience educational experiences so that they also address adult learning principles. We know that adult learners benefit from experiences that are relevant, are problem-centered (rather than content oriented), promote active learning, and provide feedback to the learner. We therefore requested that each session begin with a brief case. Having clinical examples helps learners frame the disease process, and can help demonstrate the importance of learning the material. Finally, all participants were given the opportunity to review each session, and the course in its entirety, to help us improve future programming.

Lunch sessions promoted active learning with the opportunity for interaction, and we also included case-based breakout sessions. Not only was CME accreditation provided, but Maintenance of Certification (MOC) credit was also available.

This educational offering provided a setting to hear from leaders in GI and hepatology, and for learners to gain new insights to take home and apply to the care of patients. The sections that follow provide brief summaries of the sessions from the course written by the moderators.

Please visit http://pgcourse.gastro.org/home to access the content from DDW.
 

Dr. Rose is a professor of medicine, the Senior Associate Dean for Education, University of Connecticut School of Medicine, Farmington, and the 2017 AGA Postgraduate Course Director. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.

 

I provided an update on existing, new, and upcoming medical therapies for Crohn’s disease (CD) and ulcerative colitis (UC), with a focus on studies presented at Digestive Disease Week^® 2017.

In one study of over 13,000 inflammatory bowel disease (IBD) patients in Medicare/Medicaid databases, it was found that among those treated with corticosteroids in the previous year, patients started on a tumor necrosis factor (TNF) inhibitor within the next year had mortality rates that were at least 22% lower than those of patients treated with prolonged corticosteroids over the next 12 months (Gastroenterology. 2017;152[5 Suppl 1]:S65-5). Initial results of the CALM study were presented, comparing a treat-to-target (T2T) algorithmic medical escalation approach in moderate to severe CD to a more conventional approach. Medical therapy was primarily adalimumab based and was escalated based on “success criteria,” which included not only symptomatic remission but also normalization of serum C-reactive protein and fecal calprotectin. At week 48, the rate of endoscopic remission was significantly higher (45.9%) in the T2T group than in conventionally managed patients (30.3%, P = .01), thus demonstrating the superiority of a T2T approach (Gastroenterology 2017;152[5 Suppl 1]:S155).

After several years of discussing the advent of biosimilars, one has arrived in the United States, infliximab-dyyb (Inflectra^®, Pfizer). This molecule was approved on the basis of a phase 3 trial in rheumatoid arthritis and a pharmacokinetic trial in psoriasis, and approval was extrapolated to most approved indications including IBD. Concerns had been raised that, despite the rigorous approval process, there might be subtle differences in biosimilars leading to suboptimal efficacy or to less favorable safety. A phase 3 trial of infliximab-dyyb in moderate to severe CD showed practically identical efficacy and safety compared with originator infliximab (Gastroenterology. 2017;152[5 Suppl 1]:S65). Another study compared switching from originator to infliximab-dyyb to continuation of originator infliximab among patients with a variety of conditions including IBD, and overall, there were no significant differences in clinical worsening between the “switchers” and those continued on the originator compound (Gastroenterology 2017;152[5 Suppl 1]:S65-6).

Ustekinumab is a monoclonal antibody to interleukins 12 and 23, and was approved for moderate to severe CD last year on the basis of the pivotal UNITI-1, UNITI-2, and IM-UNITI trials (N Engl J Med. 2016;375:1946-60). A weight-based intravenous loading dose was shown to be effective at inducing clinical response in both patients who had failed or were intolerant to anti-TNF therapy and those who had not. The responders in both induction trials were randomized to two subcutaneous doses of ustekinumab or placebo, and at the end of the 44-week trial, the drug met multiple efficacy endpoints, including clinical remission, clinical response, steroid-free remission, and sustained clinical remission. In another abstract, the rate of tuberculosis reactivation within the clinical development program of ustekinumab across all indications (6,581 patients, over 12,000 patient-years of follow-up) was significantly lower at 0.02 cases per 100 patient-years compared with the rates seen in the golimumab (0.24 per 100) and infliximab (0.39 per 100) development programs (Gastroenterology 2017;152[5 Suppl 1]:S596), illustrating that the safety profile of ustekinumab may be significantly different from that of anti-TNF agents.

Tofacitinib, which inhibits mainly JAK1 and JAK3 receptors, is an emergent oral small molecule drug for UC. Three phase 3 randomized placebo-controlled trials (OCTAVE-1, OCTAVE-2, and OCTAVE Sustain) of tofacitinib treatment in moderately to severely active UC patients have been recently published (N Engl J Med. 2017;376:1723-36). The rates of clinical remission at week 8 were significantly greater in patients who were treated with 10 mg tofacitinib than placebo in both induction trials, and results were similar regardless of anti-TNF exposure status. Clinical responders in the induction studies were randomized to placebo or two doses of tofacitinib. At week 52, remission rates were significantly higher in the patients treated with 10 mg tofacitinib twice daily and 5 mg tofacitinib twice daily than those receiving placebo. The percentages of tofacitinib-treated patients who achieved mucosal healing were significantly greater than those in the placebo group. Serious infections occurred significantly more frequently in the tofacitinib than placebo group during induction, but not during maintenance. However, rates of herpes zoster were higher with maintenance therapy at 10 mg twice daily (5.1%) than with placebo (0.5%). A recently published phase 2 study of filgotinib, a selective JAK1 inhibitor, reported that the remission rate at week 10 was significantly higher in active CD patients receiving 200 mg of filgotinib daily than in those receiving placebo (Lancet 2017;389:266-75). A phase 2 trial of another selective JAK1 inhibitor, upadacitinib (ABT-494), for induction therapy in CD patients with a history of failure or intolerance to TNF-antagonists, was presented at DDW (Gastroenterology 2017;152[5 Suppl 1]:S1308-9). Higher rates of clinical remission at week 16 were seen in patients on 6 mg upadacitinib twice daily than placebo, and several doses of upadacitinib were significantly better than placebo for inducing endoscopic remission at week 12 or 16. Serious adverse events were seen in 9%-15% of CD patients treated with these two agents (vs. 4%-5% in placebo-treated patients).

Smad7 regulates the signaling of transforming growth factor (TGF)-beta1, an anti-inflammatory cytokine. Mongersen is an orally delivered anti-sense oligonucleotide that inhibits Smad7 and restores TGF-beta1 signaling, and is being developed for CD. The efficacy of induction therapy for active CD patients with limited active disease (terminal ileum or proximal colon) was demonstrated in a phase 2 study (N Engl J Med. 2015;372:1104-13). Interestingly, this study showed significantly higher rates of clinical remission at day 15 with mongersen. However, there were no endoscopic data available in this trial, baseline serum C-reactive protein concentrations were low, and did not decrease significantly. This drug appears to be well tolerated, and serious adverse events were not significantly higher than for placebo. In a phase 1b study, correlations between clinical and endoscopic outcomes were explored, and among 52 CD patients, SES-CD reductions of at least 25% at week 12 were seen in 37% of mongersen-treated patients (Gastroenterology. 2017;152[5 Suppl 1]:S198).

In summary, the future of IBD medical therapy is bright due to the recent introduction of therapies with novel mechanisms of action and favorable safety profiles (e.g., vedolizumab and ustekinumab), potentially lower-cost biosimilars, and multiple compounds in the drug development pipeline.
 

 

Dr. Loftus is professor of medicine, Mayo Clinic College of Medicine, director of the Inflammatory Bowel Disease Interest Group, the division of gastroenterology and hepatology, Rochester, Minn. He made his comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

I provided an update on existing, new, and upcoming medical therapies for Crohn’s disease (CD) and ulcerative colitis (UC), with a focus on studies presented at Digestive Disease Week^® 2017.

In one study of over 13,000 inflammatory bowel disease (IBD) patients in Medicare/Medicaid databases, it was found that among those treated with corticosteroids in the previous year, patients started on a tumor necrosis factor (TNF) inhibitor within the next year had mortality rates that were at least 22% lower than those of patients treated with prolonged corticosteroids over the next 12 months (Gastroenterology. 2017;152[5 Suppl 1]:S65-5). Initial results of the CALM study were presented, comparing a treat-to-target (T2T) algorithmic medical escalation approach in moderate to severe CD to a more conventional approach. Medical therapy was primarily adalimumab based and was escalated based on “success criteria,” which included not only symptomatic remission but also normalization of serum C-reactive protein and fecal calprotectin. At week 48, the rate of endoscopic remission was significantly higher (45.9%) in the T2T group than in conventionally managed patients (30.3%, P = .01), thus demonstrating the superiority of a T2T approach (Gastroenterology 2017;152[5 Suppl 1]:S155).

After several years of discussing the advent of biosimilars, one has arrived in the United States, infliximab-dyyb (Inflectra^®, Pfizer). This molecule was approved on the basis of a phase 3 trial in rheumatoid arthritis and a pharmacokinetic trial in psoriasis, and approval was extrapolated to most approved indications including IBD. Concerns had been raised that, despite the rigorous approval process, there might be subtle differences in biosimilars leading to suboptimal efficacy or to less favorable safety. A phase 3 trial of infliximab-dyyb in moderate to severe CD showed practically identical efficacy and safety compared with originator infliximab (Gastroenterology. 2017;152[5 Suppl 1]:S65). Another study compared switching from originator to infliximab-dyyb to continuation of originator infliximab among patients with a variety of conditions including IBD, and overall, there were no significant differences in clinical worsening between the “switchers” and those continued on the originator compound (Gastroenterology 2017;152[5 Suppl 1]:S65-6).

Ustekinumab is a monoclonal antibody to interleukins 12 and 23, and was approved for moderate to severe CD last year on the basis of the pivotal UNITI-1, UNITI-2, and IM-UNITI trials (N Engl J Med. 2016;375:1946-60). A weight-based intravenous loading dose was shown to be effective at inducing clinical response in both patients who had failed or were intolerant to anti-TNF therapy and those who had not. The responders in both induction trials were randomized to two subcutaneous doses of ustekinumab or placebo, and at the end of the 44-week trial, the drug met multiple efficacy endpoints, including clinical remission, clinical response, steroid-free remission, and sustained clinical remission. In another abstract, the rate of tuberculosis reactivation within the clinical development program of ustekinumab across all indications (6,581 patients, over 12,000 patient-years of follow-up) was significantly lower at 0.02 cases per 100 patient-years compared with the rates seen in the golimumab (0.24 per 100) and infliximab (0.39 per 100) development programs (Gastroenterology 2017;152[5 Suppl 1]:S596), illustrating that the safety profile of ustekinumab may be significantly different from that of anti-TNF agents.

Tofacitinib, which inhibits mainly JAK1 and JAK3 receptors, is an emergent oral small molecule drug for UC. Three phase 3 randomized placebo-controlled trials (OCTAVE-1, OCTAVE-2, and OCTAVE Sustain) of tofacitinib treatment in moderately to severely active UC patients have been recently published (N Engl J Med. 2017;376:1723-36). The rates of clinical remission at week 8 were significantly greater in patients who were treated with 10 mg tofacitinib than placebo in both induction trials, and results were similar regardless of anti-TNF exposure status. Clinical responders in the induction studies were randomized to placebo or two doses of tofacitinib. At week 52, remission rates were significantly higher in the patients treated with 10 mg tofacitinib twice daily and 5 mg tofacitinib twice daily than those receiving placebo. The percentages of tofacitinib-treated patients who achieved mucosal healing were significantly greater than those in the placebo group. Serious infections occurred significantly more frequently in the tofacitinib than placebo group during induction, but not during maintenance. However, rates of herpes zoster were higher with maintenance therapy at 10 mg twice daily (5.1%) than with placebo (0.5%). A recently published phase 2 study of filgotinib, a selective JAK1 inhibitor, reported that the remission rate at week 10 was significantly higher in active CD patients receiving 200 mg of filgotinib daily than in those receiving placebo (Lancet 2017;389:266-75). A phase 2 trial of another selective JAK1 inhibitor, upadacitinib (ABT-494), for induction therapy in CD patients with a history of failure or intolerance to TNF-antagonists, was presented at DDW (Gastroenterology 2017;152[5 Suppl 1]:S1308-9). Higher rates of clinical remission at week 16 were seen in patients on 6 mg upadacitinib twice daily than placebo, and several doses of upadacitinib were significantly better than placebo for inducing endoscopic remission at week 12 or 16. Serious adverse events were seen in 9%-15% of CD patients treated with these two agents (vs. 4%-5% in placebo-treated patients).

Smad7 regulates the signaling of transforming growth factor (TGF)-beta1, an anti-inflammatory cytokine. Mongersen is an orally delivered anti-sense oligonucleotide that inhibits Smad7 and restores TGF-beta1 signaling, and is being developed for CD. The efficacy of induction therapy for active CD patients with limited active disease (terminal ileum or proximal colon) was demonstrated in a phase 2 study (N Engl J Med. 2015;372:1104-13). Interestingly, this study showed significantly higher rates of clinical remission at day 15 with mongersen. However, there were no endoscopic data available in this trial, baseline serum C-reactive protein concentrations were low, and did not decrease significantly. This drug appears to be well tolerated, and serious adverse events were not significantly higher than for placebo. In a phase 1b study, correlations between clinical and endoscopic outcomes were explored, and among 52 CD patients, SES-CD reductions of at least 25% at week 12 were seen in 37% of mongersen-treated patients (Gastroenterology. 2017;152[5 Suppl 1]:S198).

In summary, the future of IBD medical therapy is bright due to the recent introduction of therapies with novel mechanisms of action and favorable safety profiles (e.g., vedolizumab and ustekinumab), potentially lower-cost biosimilars, and multiple compounds in the drug development pipeline.
 

 

Dr. Loftus is professor of medicine, Mayo Clinic College of Medicine, director of the Inflammatory Bowel Disease Interest Group, the division of gastroenterology and hepatology, Rochester, Minn. He made his comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

I provided an update on existing, new, and upcoming medical therapies for Crohn’s disease (CD) and ulcerative colitis (UC), with a focus on studies presented at Digestive Disease Week^® 2017.

In one study of over 13,000 inflammatory bowel disease (IBD) patients in Medicare/Medicaid databases, it was found that among those treated with corticosteroids in the previous year, patients started on a tumor necrosis factor (TNF) inhibitor within the next year had mortality rates that were at least 22% lower than those of patients treated with prolonged corticosteroids over the next 12 months (Gastroenterology. 2017;152[5 Suppl 1]:S65-5). Initial results of the CALM study were presented, comparing a treat-to-target (T2T) algorithmic medical escalation approach in moderate to severe CD to a more conventional approach. Medical therapy was primarily adalimumab based and was escalated based on “success criteria,” which included not only symptomatic remission but also normalization of serum C-reactive protein and fecal calprotectin. At week 48, the rate of endoscopic remission was significantly higher (45.9%) in the T2T group than in conventionally managed patients (30.3%, P = .01), thus demonstrating the superiority of a T2T approach (Gastroenterology 2017;152[5 Suppl 1]:S155).

After several years of discussing the advent of biosimilars, one has arrived in the United States, infliximab-dyyb (Inflectra^®, Pfizer). This molecule was approved on the basis of a phase 3 trial in rheumatoid arthritis and a pharmacokinetic trial in psoriasis, and approval was extrapolated to most approved indications including IBD. Concerns had been raised that, despite the rigorous approval process, there might be subtle differences in biosimilars leading to suboptimal efficacy or to less favorable safety. A phase 3 trial of infliximab-dyyb in moderate to severe CD showed practically identical efficacy and safety compared with originator infliximab (Gastroenterology. 2017;152[5 Suppl 1]:S65). Another study compared switching from originator to infliximab-dyyb to continuation of originator infliximab among patients with a variety of conditions including IBD, and overall, there were no significant differences in clinical worsening between the “switchers” and those continued on the originator compound (Gastroenterology 2017;152[5 Suppl 1]:S65-6).

Ustekinumab is a monoclonal antibody to interleukins 12 and 23, and was approved for moderate to severe CD last year on the basis of the pivotal UNITI-1, UNITI-2, and IM-UNITI trials (N Engl J Med. 2016;375:1946-60). A weight-based intravenous loading dose was shown to be effective at inducing clinical response in both patients who had failed or were intolerant to anti-TNF therapy and those who had not. The responders in both induction trials were randomized to two subcutaneous doses of ustekinumab or placebo, and at the end of the 44-week trial, the drug met multiple efficacy endpoints, including clinical remission, clinical response, steroid-free remission, and sustained clinical remission. In another abstract, the rate of tuberculosis reactivation within the clinical development program of ustekinumab across all indications (6,581 patients, over 12,000 patient-years of follow-up) was significantly lower at 0.02 cases per 100 patient-years compared with the rates seen in the golimumab (0.24 per 100) and infliximab (0.39 per 100) development programs (Gastroenterology 2017;152[5 Suppl 1]:S596), illustrating that the safety profile of ustekinumab may be significantly different from that of anti-TNF agents.

Tofacitinib, which inhibits mainly JAK1 and JAK3 receptors, is an emergent oral small molecule drug for UC. Three phase 3 randomized placebo-controlled trials (OCTAVE-1, OCTAVE-2, and OCTAVE Sustain) of tofacitinib treatment in moderately to severely active UC patients have been recently published (N Engl J Med. 2017;376:1723-36). The rates of clinical remission at week 8 were significantly greater in patients who were treated with 10 mg tofacitinib than placebo in both induction trials, and results were similar regardless of anti-TNF exposure status. Clinical responders in the induction studies were randomized to placebo or two doses of tofacitinib. At week 52, remission rates were significantly higher in the patients treated with 10 mg tofacitinib twice daily and 5 mg tofacitinib twice daily than those receiving placebo. The percentages of tofacitinib-treated patients who achieved mucosal healing were significantly greater than those in the placebo group. Serious infections occurred significantly more frequently in the tofacitinib than placebo group during induction, but not during maintenance. However, rates of herpes zoster were higher with maintenance therapy at 10 mg twice daily (5.1%) than with placebo (0.5%). A recently published phase 2 study of filgotinib, a selective JAK1 inhibitor, reported that the remission rate at week 10 was significantly higher in active CD patients receiving 200 mg of filgotinib daily than in those receiving placebo (Lancet 2017;389:266-75). A phase 2 trial of another selective JAK1 inhibitor, upadacitinib (ABT-494), for induction therapy in CD patients with a history of failure or intolerance to TNF-antagonists, was presented at DDW (Gastroenterology 2017;152[5 Suppl 1]:S1308-9). Higher rates of clinical remission at week 16 were seen in patients on 6 mg upadacitinib twice daily than placebo, and several doses of upadacitinib were significantly better than placebo for inducing endoscopic remission at week 12 or 16. Serious adverse events were seen in 9%-15% of CD patients treated with these two agents (vs. 4%-5% in placebo-treated patients).

Smad7 regulates the signaling of transforming growth factor (TGF)-beta1, an anti-inflammatory cytokine. Mongersen is an orally delivered anti-sense oligonucleotide that inhibits Smad7 and restores TGF-beta1 signaling, and is being developed for CD. The efficacy of induction therapy for active CD patients with limited active disease (terminal ileum or proximal colon) was demonstrated in a phase 2 study (N Engl J Med. 2015;372:1104-13). Interestingly, this study showed significantly higher rates of clinical remission at day 15 with mongersen. However, there were no endoscopic data available in this trial, baseline serum C-reactive protein concentrations were low, and did not decrease significantly. This drug appears to be well tolerated, and serious adverse events were not significantly higher than for placebo. In a phase 1b study, correlations between clinical and endoscopic outcomes were explored, and among 52 CD patients, SES-CD reductions of at least 25% at week 12 were seen in 37% of mongersen-treated patients (Gastroenterology. 2017;152[5 Suppl 1]:S198).

In summary, the future of IBD medical therapy is bright due to the recent introduction of therapies with novel mechanisms of action and favorable safety profiles (e.g., vedolizumab and ustekinumab), potentially lower-cost biosimilars, and multiple compounds in the drug development pipeline.
 

 

Dr. Loftus is professor of medicine, Mayo Clinic College of Medicine, director of the Inflammatory Bowel Disease Interest Group, the division of gastroenterology and hepatology, Rochester, Minn. He made his comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT₄ receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.

AGA Institute

Relamorelin (RM-131) is a selective pentapeptide ghrelin receptor agonist with potent prokinetic properties. A prior phase 2a study showed that 10 microg b.i.d. relamorelin subcutaneously for 4 weeks had prokinetic activity and relieved symptoms of diabetic gastroparesis, especially in patients with vomiting at baseline.

The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.

A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T_1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.

Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.

Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT₄ receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.

AGA Institute

Relamorelin (RM-131) is a selective pentapeptide ghrelin receptor agonist with potent prokinetic properties. A prior phase 2a study showed that 10 microg b.i.d. relamorelin subcutaneously for 4 weeks had prokinetic activity and relieved symptoms of diabetic gastroparesis, especially in patients with vomiting at baseline.

The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.

A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T_1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.

Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.

Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT₄ receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.

AGA Institute

Relamorelin (RM-131) is a selective pentapeptide ghrelin receptor agonist with potent prokinetic properties. A prior phase 2a study showed that 10 microg b.i.d. relamorelin subcutaneously for 4 weeks had prokinetic activity and relieved symptoms of diabetic gastroparesis, especially in patients with vomiting at baseline.

The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.

A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T_1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.

Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.

Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Despite the availability of safe and effective vaccines for more than three decades, the 2017 World Health Organization (WHO) Global Hepatitis Report estimated that worldwide more than 250 million persons are chronically infected with hepatitis B virus (www.who.int/hepatitis/publications/global-hepatitis-report2017/). In the United States, as many as 2.2 million persons may be chronically infected but only one-third are aware of their infection. In 2015, the WHO declared that hepatitis B and C should be eliminated as public health problems by the year 2030. In March 2017, the National Academies of Science, Engineering and Medicine (NASEM) set targets for HBV elimination in the United States by 2030 as follows: 50% reduction in deaths, 45% reduction in cirrhosis, and 33% reduction in hepatocellular carcinoma (HCC) compared to 2015. For these targets, 90% of persons chronically infected need to be diagnosed, 90% of those diagnosed linked to care, and treatment initiated in 80% of those with treatment indications. In addition, new infections among children should be eliminated through complete prevention of mother-to-child transmission.

HBV vaccination, particularly when initiated in newborns, is the most effective method of preventing HBV infection and its sequelae because the risk of chronicity is around 90% when infection occurs in newborns. Countries in which universal vaccination of newborns was initiated in the 1980s have witnessed a marked decline in HBV infection as well as HBV-related HCC in children and young adults. However, while 96% of countries worldwide have initiated nationwide HBV vaccine programs for infants, global birth dose coverage is only 39%, leaving many infants susceptible to infection during the first few months of life. Recent studies showed that administration of hepatitis B immunoglobulin and HBV vaccine within 24 hours of birth is inadequate in preventing infection of infants born to carrier mothers with high viremia. Antiviral medicine administered to highly viremic mothers during the third trimester of pregnancy is necessary to completely prevent the risk of mother-to-child transmission (Hepatology. 2016;63:261-83).

For persons who are chronically infected, antiviral therapy can suppress HBV replication, reduce hepatic inflammation, reverse hepatic fibrosis, and prevent progression to cirrhosis, hepatic decompensation, and HCC. However, currently approved treatments are associated with low rates of hepatitis B surface antigen (HBsAg) clearance and decreased but continued risk of HCC. New treatments aimed at cure are desired but complete cure of HBV may not be feasible as HBV persists in the liver even in patients with serologic recovery after transient acute HBV infection.

Functional cure aimed at restoring chronic hepatitis B patients to a state akin to those with spontaneous HBsAg clearance might be a more realistic goal. With improved understanding of the biology of HBV, including recent identification of its entry receptor, better in vitro and animal models, and revival of interest in hepatitis B research, it is conceivable that combinations of antiviral targeting different steps in HBV life cyle and immunomodulatory therapies aimed to boost T-cell response to HBV and/or remove inhibitory signals can result in functional cure (HBsAg clearance) in a high percentage of patients after a finite course of treatment (Hepatology 2017; in press).

The HBV elimination goals set by WHO and NASEM are lofty, but as both organizations stated, these goals are feasible if all stakeholders make elimination of HBV a priority and allocate resources to make it happen.
 

Dr. Lok is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine, University of Michigan Health System in Ann Arbor. Her comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.