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AGA Guideline: Transient elastography in liver fibrosis, most used and most accurate
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
FROM GASTROENTEROLOGY
VIDEO: Study confirms uneven access to liver cancer treatment at VA hospitals
Only 25% of Veterans Affairs (VA) patients with potentially curable (Barcelona Clinic Liver Cancer stage 0/A) hepatocellular carcinoma received resection, transplantation, or ablative therapy, according to the results of a national retrospective cohort study published in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.040).
Furthermore, 13% of the fittest (ECOG performance status 1-2) patients received no active treatment for their hepatocellular carcinoma, Marina Serper, MD, of Corporal Michael J. Crescenz VA Medical Center, Philadelphia, and Tamar H. Taddei, MD, of VA New York Harbor Health Care System, Brooklyn, New York, wrote with their associates in Gastroenterology.
Source: American Gastroenterological Association
“Delivery of curative therapies conferred the highest survival benefit, and notable geographic and specialist variation was observed in the delivery of active treatment,” they added. “Future studies should further evaluate modifiable health system and provider-specific barriers to delivering high quality, multidisciplinary care in hepatocellular carcinoma [in order] to optimize patient outcomes.”
Hepatocellular carcinoma ranks second worldwide and fifth in the United States as a cause of cancer mortality. Gastroenterologists, hepatologists, medical oncologists, or surgeons may take primary responsibility for treatment in community settings, but little is known about how provider and health system factors affect outcomes or the likelihood of receiving active treatments, such as liver transplantation, resection, ablative or transarterial therapy, sorafenib, systemic chemotherapy, or radiation. Accordingly, the researchers reviewed medical records and demographic data from all 3,988 U.S. patients diagnosed with hepatocellular carcinoma between 2008 and 2010 who received care at 128 Veterans Affairs centers. Patients were followed through the end of 2014. Data were from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort study (Gastroenterology. 2017 Mar 7. doi: 10.1053/j.gastro.2017.02.040).
After diagnosis, most (54%) patients only underwent transarterial palliative therapy, and 24% received no cancer treatment, the researchers reported. Being treated at an academically affiliated VA hospital nearly doubled the odds of receiving active therapy (odds ratio, 1.97; 95% confidence interval, 1.6 to 2.4; P less than .001), even after the researchers controlled for race, Charlson-Deyo comorbidity, and presenting Barcelona Clinic Liver Cancer stage. Evaluation by multiple specialists also significantly increased the odds of active treatment (OR, 1.60; 95% CI, 1.15 to 2.21; P = .005), but review by a multidisciplinary tumor board did not (OR, 1.19; P = .1).
Receipt of active therapy also varied significantly by region. Compared with patients in the Northeastern United States, those in the mid-South were significantly less likely to receive active therapy (HR, 0.62; 95% CI, 0.44-0.85). Patients in the Southeast, Central, and Western United States also were less likely to receive active treatment than were those in the Northeast, but 95% CIs for these hazard ratios were nonsignificant. Virtual tumor boards could help overcome diagnostic and treatment delays, but costs, care coordination, patient factors, and compensation issues are major barriers against implementation, the investigators noted.
Overall survival was associated with active treatment of hepatocellular carcinoma, including liver transplantation (hazard ratio, 0.22; 95% CI, 0.16-0.31), liver resection (HR, 0.38; 95% CI, 0.28-0.52), ablative therapy (HR, 0.63; 95% CI, 0.52-0.76), and transarterial therapy (HR, 0.83; 95% CI, 0.74-0.92). Reduced mortality was associated with seeing a hepatologist (HR, 0.7), medical oncologist (HR, 0.82), or surgeon (HR, 0.79) within 30 days of diagnosis (P less than .001 for each). Undergoing review by a multidisciplinary tumor board was associated with significantly reduced mortality (HR, 0.83; P less than .001), said the researchers.
“Findings from the VOCAL cohort of predominantly older males with significant medical comorbidities are important in light of the aging U.S. population and a nearly 70% expected increase in cancer among older adults,” they wrote. Together, the results indicate that access to multidisciplinary and expert care “is critical for optimizing treatment choices and for maximizing survival, but that such access is non-uniform,” they noted. “Detailed national VA clinical and administrative data are a unique resource that may be tapped to facilitate development of a parsimonious set of evidence-based, patient-centered, liver cancer–specific quality measures,” they emphasized. Quality measures based on timeliness, receipt of appropriate care, survival, or patient-reported outcomes “could be applicable both within and outside the VA system.”
The study was funded by unrestricted grants from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs. The investigators had no conflicts.
The treatment of hepatocellular carcinoma (HCC) can be challenging because of the presence of underlying chronic liver disease and cirrhosis in the majority of patients. The study by Dr. Serper and colleagues evaluated the care of patients diagnosed with HCC in the Veterans Affairs (VA) system between 2008 and 2010. There are important aspects of this study worth highlighting.
First, 36% of patients presented with early-stage HCC and clearly had a better overall survival. This highlights the need for surveillance of patients with cirrhosis not only in the VA but also in other health systems. Second, only a minority of patients with early-stage HCC received curative interventions. In order to improve outcomes, patients with early stage disease should receive appropriate curative interventions. Third, gastroenterologists saw a large number of patients with HCC in the VA system, but, unfortunately, this led to less receipt of active therapy and a trend for a worse all-cause mortality, compared with hepatologists and other specialties. It is critical that gastroenterologists refer patients to specialties more adept at treating HCC in order to achieve better outcomes.
Lastly, only 34% of patients with HCC were managed via a multidisciplinary tumor conference. Importantly, these patients had an increased probability of receipt of active treatment and a 17% reduction in all-cause mortality. Our group has shown that a multidisciplinary approach to treating HCC improves overall survival. It is critical that medical centers develop a multidisciplinary treatment approach to HCC.
Jorge A. Marrero, MD, MS, AGAF, is professor of medicine and medical director for liver transplantation at UT Southwestern Medical Center Dallas. He has no conflicts of interest to report regarding this manuscript or commentary.
The treatment of hepatocellular carcinoma (HCC) can be challenging because of the presence of underlying chronic liver disease and cirrhosis in the majority of patients. The study by Dr. Serper and colleagues evaluated the care of patients diagnosed with HCC in the Veterans Affairs (VA) system between 2008 and 2010. There are important aspects of this study worth highlighting.
First, 36% of patients presented with early-stage HCC and clearly had a better overall survival. This highlights the need for surveillance of patients with cirrhosis not only in the VA but also in other health systems. Second, only a minority of patients with early-stage HCC received curative interventions. In order to improve outcomes, patients with early stage disease should receive appropriate curative interventions. Third, gastroenterologists saw a large number of patients with HCC in the VA system, but, unfortunately, this led to less receipt of active therapy and a trend for a worse all-cause mortality, compared with hepatologists and other specialties. It is critical that gastroenterologists refer patients to specialties more adept at treating HCC in order to achieve better outcomes.
Lastly, only 34% of patients with HCC were managed via a multidisciplinary tumor conference. Importantly, these patients had an increased probability of receipt of active treatment and a 17% reduction in all-cause mortality. Our group has shown that a multidisciplinary approach to treating HCC improves overall survival. It is critical that medical centers develop a multidisciplinary treatment approach to HCC.
Jorge A. Marrero, MD, MS, AGAF, is professor of medicine and medical director for liver transplantation at UT Southwestern Medical Center Dallas. He has no conflicts of interest to report regarding this manuscript or commentary.
The treatment of hepatocellular carcinoma (HCC) can be challenging because of the presence of underlying chronic liver disease and cirrhosis in the majority of patients. The study by Dr. Serper and colleagues evaluated the care of patients diagnosed with HCC in the Veterans Affairs (VA) system between 2008 and 2010. There are important aspects of this study worth highlighting.
First, 36% of patients presented with early-stage HCC and clearly had a better overall survival. This highlights the need for surveillance of patients with cirrhosis not only in the VA but also in other health systems. Second, only a minority of patients with early-stage HCC received curative interventions. In order to improve outcomes, patients with early stage disease should receive appropriate curative interventions. Third, gastroenterologists saw a large number of patients with HCC in the VA system, but, unfortunately, this led to less receipt of active therapy and a trend for a worse all-cause mortality, compared with hepatologists and other specialties. It is critical that gastroenterologists refer patients to specialties more adept at treating HCC in order to achieve better outcomes.
Lastly, only 34% of patients with HCC were managed via a multidisciplinary tumor conference. Importantly, these patients had an increased probability of receipt of active treatment and a 17% reduction in all-cause mortality. Our group has shown that a multidisciplinary approach to treating HCC improves overall survival. It is critical that medical centers develop a multidisciplinary treatment approach to HCC.
Jorge A. Marrero, MD, MS, AGAF, is professor of medicine and medical director for liver transplantation at UT Southwestern Medical Center Dallas. He has no conflicts of interest to report regarding this manuscript or commentary.
Only 25% of Veterans Affairs (VA) patients with potentially curable (Barcelona Clinic Liver Cancer stage 0/A) hepatocellular carcinoma received resection, transplantation, or ablative therapy, according to the results of a national retrospective cohort study published in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.040).
Furthermore, 13% of the fittest (ECOG performance status 1-2) patients received no active treatment for their hepatocellular carcinoma, Marina Serper, MD, of Corporal Michael J. Crescenz VA Medical Center, Philadelphia, and Tamar H. Taddei, MD, of VA New York Harbor Health Care System, Brooklyn, New York, wrote with their associates in Gastroenterology.
Source: American Gastroenterological Association
“Delivery of curative therapies conferred the highest survival benefit, and notable geographic and specialist variation was observed in the delivery of active treatment,” they added. “Future studies should further evaluate modifiable health system and provider-specific barriers to delivering high quality, multidisciplinary care in hepatocellular carcinoma [in order] to optimize patient outcomes.”
Hepatocellular carcinoma ranks second worldwide and fifth in the United States as a cause of cancer mortality. Gastroenterologists, hepatologists, medical oncologists, or surgeons may take primary responsibility for treatment in community settings, but little is known about how provider and health system factors affect outcomes or the likelihood of receiving active treatments, such as liver transplantation, resection, ablative or transarterial therapy, sorafenib, systemic chemotherapy, or radiation. Accordingly, the researchers reviewed medical records and demographic data from all 3,988 U.S. patients diagnosed with hepatocellular carcinoma between 2008 and 2010 who received care at 128 Veterans Affairs centers. Patients were followed through the end of 2014. Data were from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort study (Gastroenterology. 2017 Mar 7. doi: 10.1053/j.gastro.2017.02.040).
After diagnosis, most (54%) patients only underwent transarterial palliative therapy, and 24% received no cancer treatment, the researchers reported. Being treated at an academically affiliated VA hospital nearly doubled the odds of receiving active therapy (odds ratio, 1.97; 95% confidence interval, 1.6 to 2.4; P less than .001), even after the researchers controlled for race, Charlson-Deyo comorbidity, and presenting Barcelona Clinic Liver Cancer stage. Evaluation by multiple specialists also significantly increased the odds of active treatment (OR, 1.60; 95% CI, 1.15 to 2.21; P = .005), but review by a multidisciplinary tumor board did not (OR, 1.19; P = .1).
Receipt of active therapy also varied significantly by region. Compared with patients in the Northeastern United States, those in the mid-South were significantly less likely to receive active therapy (HR, 0.62; 95% CI, 0.44-0.85). Patients in the Southeast, Central, and Western United States also were less likely to receive active treatment than were those in the Northeast, but 95% CIs for these hazard ratios were nonsignificant. Virtual tumor boards could help overcome diagnostic and treatment delays, but costs, care coordination, patient factors, and compensation issues are major barriers against implementation, the investigators noted.
Overall survival was associated with active treatment of hepatocellular carcinoma, including liver transplantation (hazard ratio, 0.22; 95% CI, 0.16-0.31), liver resection (HR, 0.38; 95% CI, 0.28-0.52), ablative therapy (HR, 0.63; 95% CI, 0.52-0.76), and transarterial therapy (HR, 0.83; 95% CI, 0.74-0.92). Reduced mortality was associated with seeing a hepatologist (HR, 0.7), medical oncologist (HR, 0.82), or surgeon (HR, 0.79) within 30 days of diagnosis (P less than .001 for each). Undergoing review by a multidisciplinary tumor board was associated with significantly reduced mortality (HR, 0.83; P less than .001), said the researchers.
“Findings from the VOCAL cohort of predominantly older males with significant medical comorbidities are important in light of the aging U.S. population and a nearly 70% expected increase in cancer among older adults,” they wrote. Together, the results indicate that access to multidisciplinary and expert care “is critical for optimizing treatment choices and for maximizing survival, but that such access is non-uniform,” they noted. “Detailed national VA clinical and administrative data are a unique resource that may be tapped to facilitate development of a parsimonious set of evidence-based, patient-centered, liver cancer–specific quality measures,” they emphasized. Quality measures based on timeliness, receipt of appropriate care, survival, or patient-reported outcomes “could be applicable both within and outside the VA system.”
The study was funded by unrestricted grants from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs. The investigators had no conflicts.
Only 25% of Veterans Affairs (VA) patients with potentially curable (Barcelona Clinic Liver Cancer stage 0/A) hepatocellular carcinoma received resection, transplantation, or ablative therapy, according to the results of a national retrospective cohort study published in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.040).
Furthermore, 13% of the fittest (ECOG performance status 1-2) patients received no active treatment for their hepatocellular carcinoma, Marina Serper, MD, of Corporal Michael J. Crescenz VA Medical Center, Philadelphia, and Tamar H. Taddei, MD, of VA New York Harbor Health Care System, Brooklyn, New York, wrote with their associates in Gastroenterology.
Source: American Gastroenterological Association
“Delivery of curative therapies conferred the highest survival benefit, and notable geographic and specialist variation was observed in the delivery of active treatment,” they added. “Future studies should further evaluate modifiable health system and provider-specific barriers to delivering high quality, multidisciplinary care in hepatocellular carcinoma [in order] to optimize patient outcomes.”
Hepatocellular carcinoma ranks second worldwide and fifth in the United States as a cause of cancer mortality. Gastroenterologists, hepatologists, medical oncologists, or surgeons may take primary responsibility for treatment in community settings, but little is known about how provider and health system factors affect outcomes or the likelihood of receiving active treatments, such as liver transplantation, resection, ablative or transarterial therapy, sorafenib, systemic chemotherapy, or radiation. Accordingly, the researchers reviewed medical records and demographic data from all 3,988 U.S. patients diagnosed with hepatocellular carcinoma between 2008 and 2010 who received care at 128 Veterans Affairs centers. Patients were followed through the end of 2014. Data were from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort study (Gastroenterology. 2017 Mar 7. doi: 10.1053/j.gastro.2017.02.040).
After diagnosis, most (54%) patients only underwent transarterial palliative therapy, and 24% received no cancer treatment, the researchers reported. Being treated at an academically affiliated VA hospital nearly doubled the odds of receiving active therapy (odds ratio, 1.97; 95% confidence interval, 1.6 to 2.4; P less than .001), even after the researchers controlled for race, Charlson-Deyo comorbidity, and presenting Barcelona Clinic Liver Cancer stage. Evaluation by multiple specialists also significantly increased the odds of active treatment (OR, 1.60; 95% CI, 1.15 to 2.21; P = .005), but review by a multidisciplinary tumor board did not (OR, 1.19; P = .1).
Receipt of active therapy also varied significantly by region. Compared with patients in the Northeastern United States, those in the mid-South were significantly less likely to receive active therapy (HR, 0.62; 95% CI, 0.44-0.85). Patients in the Southeast, Central, and Western United States also were less likely to receive active treatment than were those in the Northeast, but 95% CIs for these hazard ratios were nonsignificant. Virtual tumor boards could help overcome diagnostic and treatment delays, but costs, care coordination, patient factors, and compensation issues are major barriers against implementation, the investigators noted.
Overall survival was associated with active treatment of hepatocellular carcinoma, including liver transplantation (hazard ratio, 0.22; 95% CI, 0.16-0.31), liver resection (HR, 0.38; 95% CI, 0.28-0.52), ablative therapy (HR, 0.63; 95% CI, 0.52-0.76), and transarterial therapy (HR, 0.83; 95% CI, 0.74-0.92). Reduced mortality was associated with seeing a hepatologist (HR, 0.7), medical oncologist (HR, 0.82), or surgeon (HR, 0.79) within 30 days of diagnosis (P less than .001 for each). Undergoing review by a multidisciplinary tumor board was associated with significantly reduced mortality (HR, 0.83; P less than .001), said the researchers.
“Findings from the VOCAL cohort of predominantly older males with significant medical comorbidities are important in light of the aging U.S. population and a nearly 70% expected increase in cancer among older adults,” they wrote. Together, the results indicate that access to multidisciplinary and expert care “is critical for optimizing treatment choices and for maximizing survival, but that such access is non-uniform,” they noted. “Detailed national VA clinical and administrative data are a unique resource that may be tapped to facilitate development of a parsimonious set of evidence-based, patient-centered, liver cancer–specific quality measures,” they emphasized. Quality measures based on timeliness, receipt of appropriate care, survival, or patient-reported outcomes “could be applicable both within and outside the VA system.”
The study was funded by unrestricted grants from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs. The investigators had no conflicts.
FROM GASTROENTEROLOGY
Key clinical point: Undertreatment of hepatocellular carcinoma was common within the Veterans Affairs system, and varied by geographic region.
Major finding: Only 25% of Barcelona Clinic Liver Cancer stage 0/A patients received potentially curative therapies. Those in the mid-South were significantly less likely to receive active treatment than were those in the Northeast (HR, 0.62; 95% CI, 0.44-0.85). In an adjusted model, treatment at an academically affiliated VA hospital nearly doubled the odds of receiving active therapy (odds ratio, 1.97; P less than .001).
Data source: A national, retrospective cohort study of all 3,988 patients who were diagnosed with hepatocellular carcinoma between 2008 and 2010 and received care through Veterans Affairs.
Disclosures: The study was funded by unrestricted grants from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs. The investigators had no conflicts.
VIDEO: Study estimates prevalence of pediatric celiac disease, autoimmunity
By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.
“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.
Source: American Gastroenterological Association
About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.
By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.
These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.
Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”
The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
This study calls into question the incidence of celiac disease in the modern pediatric population and, by extension, future prevalence in adults. This is a unique prospective cohort study that followed children over a decade and a half and estimated a cumulative incidence of celiac disease of 3.1% by age 15. In sharp contrast, previous retrospective population-based studies estimated a prevalence of approximately 0.75%-1% in adult and pediatric populations. A recent publication by the United States Preventive Services Task Force used the previously accepted prevalence estimates to recommend against routine screening for celiac disease in the asymptomatic general population as well as targeted screening in those at higher risk. Increases in disease incidence as reported by the current study may call these recommendations into question, particularly in young children where cumulative incidence was high and potential for treatment benefit is substantial.
Dawn Wiese Adams, MD, MS, is assistant professor, director of celiac clinic, in the department of gastroenterology, hepatology, and nutrition, Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.
This study calls into question the incidence of celiac disease in the modern pediatric population and, by extension, future prevalence in adults. This is a unique prospective cohort study that followed children over a decade and a half and estimated a cumulative incidence of celiac disease of 3.1% by age 15. In sharp contrast, previous retrospective population-based studies estimated a prevalence of approximately 0.75%-1% in adult and pediatric populations. A recent publication by the United States Preventive Services Task Force used the previously accepted prevalence estimates to recommend against routine screening for celiac disease in the asymptomatic general population as well as targeted screening in those at higher risk. Increases in disease incidence as reported by the current study may call these recommendations into question, particularly in young children where cumulative incidence was high and potential for treatment benefit is substantial.
Dawn Wiese Adams, MD, MS, is assistant professor, director of celiac clinic, in the department of gastroenterology, hepatology, and nutrition, Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.
This study calls into question the incidence of celiac disease in the modern pediatric population and, by extension, future prevalence in adults. This is a unique prospective cohort study that followed children over a decade and a half and estimated a cumulative incidence of celiac disease of 3.1% by age 15. In sharp contrast, previous retrospective population-based studies estimated a prevalence of approximately 0.75%-1% in adult and pediatric populations. A recent publication by the United States Preventive Services Task Force used the previously accepted prevalence estimates to recommend against routine screening for celiac disease in the asymptomatic general population as well as targeted screening in those at higher risk. Increases in disease incidence as reported by the current study may call these recommendations into question, particularly in young children where cumulative incidence was high and potential for treatment benefit is substantial.
Dawn Wiese Adams, MD, MS, is assistant professor, director of celiac clinic, in the department of gastroenterology, hepatology, and nutrition, Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.
By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.
“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.
Source: American Gastroenterological Association
About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.
By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.
These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.
Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”
The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
By age 15 years, 3.1% of adolescents in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity, according to a 20-year prospective longitudinal study.
“Although more than 5% of children may experience a period of celiac disease autoimmunity [CDA], not all develop celiac disease [CD] or require gluten-free diets,” Edwin Liu, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado (Aurora, Colo.), wrote with his associates in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.02.002). Most celiac autoimmunity probably develops before age 10, “which informs future efforts for universal screening,” they added.
Source: American Gastroenterological Association
About 40% of the general population has the HLA-DQ2 or DQ8 risk genotypes for celiac disease [CD], but little is known about rates of celiac disease among children in the United States, the researchers said. To help fill this gap, they analyzed celiac-risk HLA genotypes for 31,766 infants born between 1993 and 2004 from the Diabetes Autoimmunity Study in the Young. The 1,339 children with HLA risk genotypes were followed for up to 20 years.
By age 15 years, 66 of these children (4.9%) had developed tissue transglutaminase autoantibodies (tTGA) consistent with CDA, and also met criteria for CD, the researchers said. Another 46 (3.4%) children developed only CDA, of whom 46% experienced spontaneous resolution of tTGA seropositivity without treatment. By using genotype-specific risk weighting for population frequencies of HLA, the researchers estimated that 2.4% of the general population of Denver had CDA by age 5 years, 4.3% had CDA by age 10 years, and 5.1% had CDA by age 15 years. Estimated rates of CD were 1.6%, 2.8%, and 3.1%, respectively.
These findings suggest a significant rise in the incidence of CD compared with historical estimates in the United States, and reflect recent studies “using different approaches in North America,” the researchers said. Reasons for the “dramatic increase” are unknown, but environmental causes seem likely, especially given the absence of identified genetic differences and marked changes in the prevalence of CD during the past 2 decades, they added.
Several other reports have documented fluctuating and transient tTGA antibodies in children, the researchers noted. Awareness of transient CD autoantibodies might limit public acceptance of universal screening programs for CD, they said. “Continued long-term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events,” they added. “At present, low positive tTGA results should be interpreted with caution, and do not necessarily indicate need for biopsy or for treatment.”
The study did not include the DR5/DR7 risk genotype, which accounts for less than 5% of CD cases. The study also did not account for the estimated 2.5% of the general population that has DR3/DR7, which can be considered high risk, the researchers said. Thus, the study is conservative and might underestimate the real incidence of CD or CDA, they added.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
Key clinical point: The presence of celiac disease autoimmunity does not predict universal progression to celiac disease.
Major finding: By age 15 years, an estimated 3.1% of children in Denver developed celiac disease, and another 2% developed a lesser degree of celiac disease autoimmunity that often resolved spontaneously without treatment.
Data source: A 20-year prospective study of 1,339 children with genetic risk factors for celiac disease, with extrapolation based on the prevalence of human leukocyte antigen genotypes in the general population.
Disclosures: The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
VIDEO: Occult cancers contribute to GI bleeding in anticoagulated patients
Occult cancers accounted for one in about every 12 major gastrointestinal bleeding events among patients taking warfarin or dabigatran for atrial fibrillation, according to a retrospective analysis of data from a randomized prospective trial reported in the May issue of Clinical Gastroenterology and Hepatology (2017. doi: org/10.1016/j.cgh.2016.10.011).
These bleeding events caused similarly significant morbidity among patients taking either drug, Kathryn F. Flack, MD, of Icahn School of Medicine at Mount Sinai in New York and her associates wrote. “Patients bleeding from cancer required a mean of approximately 10 nights in the hospital, and approximately one-fourth required intensive care, but 0 of 44 died as a direct result of the bleeding,” the researchers reported. They hoped the specific dabigatran reversal agent, idarucizumab (Praxbind), will improve bleeding outcomes in patients receiving dabigatran.
Source: American Gastroenterological Association
Major gastrointestinal bleeding (MGIB) is the first sign of occult malignancy in certain patients receiving anticoagulation therapy. Starting an anticoagulant is a type of “stress test” that can reveal an occult cancer, the researchers said. Although dabigatran etexilate (Pradaxa) is generally safe and effective, a twice-daily, 150-mg dose of this direct oral anticoagulant slightly increased MGIB, compared with a lower dose in the international, multicenter RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial (N Engl J Med. 2009;361:1139-51). Furthermore, unlike warfarin, dabigatran therapy places active anticoagulant within the luminal gastrointestinal tract, which “might promote bleeding from friable gastrointestinal cancers,” the investigators noted. To explore this possibility, they evaluated 546 unique MGIB events among RE-LY patients.
Medical chart reviews identified 44 (8.1%) MGIB events resulting from occult gastrointestinal cancers. Cancer accounted for similar proportions of MGIB among warfarin and dabigatran recipients (8.5% and 6.8%; P = .6). Nearly all cancers were colorectal or gastric, except for one case each of ampullary cancer, renal cell carcinoma, and melanoma that had metastasized to the luminal gastrointestinal tract. Colorectal cancer accounted for 80% of cancer-related MGIB overall, including 88% in the dabigatran group and 50% in the warfarin group (P = .02). Conversely, warfarin recipients had more MGIB associated with gastric cancer (50%) than did dabigatran recipients (2.9%; P = .001).
Short-term outcomes of MGIB associated with cancer did not vary by anticoagulant, the investigators said. There were no deaths, but two (4.5%) MGIB events required emergency endoscopic treatment, one (2.3%) required emergency surgery, and 33 (75%) required at least one red blood cell transfusion. Compared with patients whose MGIB was unrelated to cancer, those with cancer were more likely to bleed for more than 7 days (27.3% vs. 63.6%; P less than .001). Patients with occult cancer also developed MGIB sooner after starting anticoagulation (223 vs. 343 days; P = .003), but time to bleeding did not significantly vary by type of anticoagulant.
“Most prior studies on cancer bleeding have been case reports and case series in patients receiving warfarin,” the investigators wrote. “Our study is relevant because of the increasing prevalence of atrial fibrillation and anticoagulation in the aging global population, the increasing prescription of direct oral anticoagulants, and the morbidity, mortality, and complex decision making associated with MGIB and especially cancer-related MGIB in patients receiving anticoagulation therapy.”
The RE-LY trial was sponsored by Boehringer Ingelheim . Dr. Flack reported no conflicts of interest. Senior author James Aisenberg, MD, disclosed advisory board and consulting relationships with Boehringer Ingelheim and Portola Pharmaceuticals. Five other coinvestigators disclosed ties to several pharmaceutical companies, and two coinvestigators reported employment with Boehringer Ingelheim. The other coinvestigators had no conflicts.
Dr. Flack and her colleagues should be congratulated for providing important data as they reviewed 546 major GI bleeding events from a large randomized prospective trial of long-term anticoagulation in subjects with AF. They found that 1 in every 12 major GI bleeding events in patients on warfarin or dabigatran was associated with an occult cancer; colorectal cancer being the most common.
How will these results help us in clinical practice? First, when faced with GI bleeding in AF subjects on anticoagulants, a proactive diagnostic approach is needed for the search for a potential luminal GI malignancy; whether screening for GI malignancy before initiating anticoagulants is beneficial requires prospective studies with cost analysis. Second, cancer-related GI bleeding in dabigatran users occurs earlier than noncancer-related bleeding. Given that a fraction of GI bleeding events were not investigated, one cannot exclude the possibility of undiagnosed luminal GI cancers in the comparator group. Third, cancer-related bleeding is associated with prolonged hospital stay. We should seize the opportunity to study the effects of this double-edged sword; anticoagulants may help us reveal occult malignancy, but more importantly, we need to determine whether dabigatranreversal agent idarucizumab can improve bleeding outcomes in patients on dabigatran presenting with cancer-related bleeding.
Siew C. Ng, MD, PhD, AGAF, is professor at the department of medicine and therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong. She has no conflicts of interest.
Dr. Flack and her colleagues should be congratulated for providing important data as they reviewed 546 major GI bleeding events from a large randomized prospective trial of long-term anticoagulation in subjects with AF. They found that 1 in every 12 major GI bleeding events in patients on warfarin or dabigatran was associated with an occult cancer; colorectal cancer being the most common.
How will these results help us in clinical practice? First, when faced with GI bleeding in AF subjects on anticoagulants, a proactive diagnostic approach is needed for the search for a potential luminal GI malignancy; whether screening for GI malignancy before initiating anticoagulants is beneficial requires prospective studies with cost analysis. Second, cancer-related GI bleeding in dabigatran users occurs earlier than noncancer-related bleeding. Given that a fraction of GI bleeding events were not investigated, one cannot exclude the possibility of undiagnosed luminal GI cancers in the comparator group. Third, cancer-related bleeding is associated with prolonged hospital stay. We should seize the opportunity to study the effects of this double-edged sword; anticoagulants may help us reveal occult malignancy, but more importantly, we need to determine whether dabigatranreversal agent idarucizumab can improve bleeding outcomes in patients on dabigatran presenting with cancer-related bleeding.
Siew C. Ng, MD, PhD, AGAF, is professor at the department of medicine and therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong. She has no conflicts of interest.
Dr. Flack and her colleagues should be congratulated for providing important data as they reviewed 546 major GI bleeding events from a large randomized prospective trial of long-term anticoagulation in subjects with AF. They found that 1 in every 12 major GI bleeding events in patients on warfarin or dabigatran was associated with an occult cancer; colorectal cancer being the most common.
How will these results help us in clinical practice? First, when faced with GI bleeding in AF subjects on anticoagulants, a proactive diagnostic approach is needed for the search for a potential luminal GI malignancy; whether screening for GI malignancy before initiating anticoagulants is beneficial requires prospective studies with cost analysis. Second, cancer-related GI bleeding in dabigatran users occurs earlier than noncancer-related bleeding. Given that a fraction of GI bleeding events were not investigated, one cannot exclude the possibility of undiagnosed luminal GI cancers in the comparator group. Third, cancer-related bleeding is associated with prolonged hospital stay. We should seize the opportunity to study the effects of this double-edged sword; anticoagulants may help us reveal occult malignancy, but more importantly, we need to determine whether dabigatranreversal agent idarucizumab can improve bleeding outcomes in patients on dabigatran presenting with cancer-related bleeding.
Siew C. Ng, MD, PhD, AGAF, is professor at the department of medicine and therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong. She has no conflicts of interest.
Occult cancers accounted for one in about every 12 major gastrointestinal bleeding events among patients taking warfarin or dabigatran for atrial fibrillation, according to a retrospective analysis of data from a randomized prospective trial reported in the May issue of Clinical Gastroenterology and Hepatology (2017. doi: org/10.1016/j.cgh.2016.10.011).
These bleeding events caused similarly significant morbidity among patients taking either drug, Kathryn F. Flack, MD, of Icahn School of Medicine at Mount Sinai in New York and her associates wrote. “Patients bleeding from cancer required a mean of approximately 10 nights in the hospital, and approximately one-fourth required intensive care, but 0 of 44 died as a direct result of the bleeding,” the researchers reported. They hoped the specific dabigatran reversal agent, idarucizumab (Praxbind), will improve bleeding outcomes in patients receiving dabigatran.
Source: American Gastroenterological Association
Major gastrointestinal bleeding (MGIB) is the first sign of occult malignancy in certain patients receiving anticoagulation therapy. Starting an anticoagulant is a type of “stress test” that can reveal an occult cancer, the researchers said. Although dabigatran etexilate (Pradaxa) is generally safe and effective, a twice-daily, 150-mg dose of this direct oral anticoagulant slightly increased MGIB, compared with a lower dose in the international, multicenter RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial (N Engl J Med. 2009;361:1139-51). Furthermore, unlike warfarin, dabigatran therapy places active anticoagulant within the luminal gastrointestinal tract, which “might promote bleeding from friable gastrointestinal cancers,” the investigators noted. To explore this possibility, they evaluated 546 unique MGIB events among RE-LY patients.
Medical chart reviews identified 44 (8.1%) MGIB events resulting from occult gastrointestinal cancers. Cancer accounted for similar proportions of MGIB among warfarin and dabigatran recipients (8.5% and 6.8%; P = .6). Nearly all cancers were colorectal or gastric, except for one case each of ampullary cancer, renal cell carcinoma, and melanoma that had metastasized to the luminal gastrointestinal tract. Colorectal cancer accounted for 80% of cancer-related MGIB overall, including 88% in the dabigatran group and 50% in the warfarin group (P = .02). Conversely, warfarin recipients had more MGIB associated with gastric cancer (50%) than did dabigatran recipients (2.9%; P = .001).
Short-term outcomes of MGIB associated with cancer did not vary by anticoagulant, the investigators said. There were no deaths, but two (4.5%) MGIB events required emergency endoscopic treatment, one (2.3%) required emergency surgery, and 33 (75%) required at least one red blood cell transfusion. Compared with patients whose MGIB was unrelated to cancer, those with cancer were more likely to bleed for more than 7 days (27.3% vs. 63.6%; P less than .001). Patients with occult cancer also developed MGIB sooner after starting anticoagulation (223 vs. 343 days; P = .003), but time to bleeding did not significantly vary by type of anticoagulant.
“Most prior studies on cancer bleeding have been case reports and case series in patients receiving warfarin,” the investigators wrote. “Our study is relevant because of the increasing prevalence of atrial fibrillation and anticoagulation in the aging global population, the increasing prescription of direct oral anticoagulants, and the morbidity, mortality, and complex decision making associated with MGIB and especially cancer-related MGIB in patients receiving anticoagulation therapy.”
The RE-LY trial was sponsored by Boehringer Ingelheim . Dr. Flack reported no conflicts of interest. Senior author James Aisenberg, MD, disclosed advisory board and consulting relationships with Boehringer Ingelheim and Portola Pharmaceuticals. Five other coinvestigators disclosed ties to several pharmaceutical companies, and two coinvestigators reported employment with Boehringer Ingelheim. The other coinvestigators had no conflicts.
Occult cancers accounted for one in about every 12 major gastrointestinal bleeding events among patients taking warfarin or dabigatran for atrial fibrillation, according to a retrospective analysis of data from a randomized prospective trial reported in the May issue of Clinical Gastroenterology and Hepatology (2017. doi: org/10.1016/j.cgh.2016.10.011).
These bleeding events caused similarly significant morbidity among patients taking either drug, Kathryn F. Flack, MD, of Icahn School of Medicine at Mount Sinai in New York and her associates wrote. “Patients bleeding from cancer required a mean of approximately 10 nights in the hospital, and approximately one-fourth required intensive care, but 0 of 44 died as a direct result of the bleeding,” the researchers reported. They hoped the specific dabigatran reversal agent, idarucizumab (Praxbind), will improve bleeding outcomes in patients receiving dabigatran.
Source: American Gastroenterological Association
Major gastrointestinal bleeding (MGIB) is the first sign of occult malignancy in certain patients receiving anticoagulation therapy. Starting an anticoagulant is a type of “stress test” that can reveal an occult cancer, the researchers said. Although dabigatran etexilate (Pradaxa) is generally safe and effective, a twice-daily, 150-mg dose of this direct oral anticoagulant slightly increased MGIB, compared with a lower dose in the international, multicenter RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial (N Engl J Med. 2009;361:1139-51). Furthermore, unlike warfarin, dabigatran therapy places active anticoagulant within the luminal gastrointestinal tract, which “might promote bleeding from friable gastrointestinal cancers,” the investigators noted. To explore this possibility, they evaluated 546 unique MGIB events among RE-LY patients.
Medical chart reviews identified 44 (8.1%) MGIB events resulting from occult gastrointestinal cancers. Cancer accounted for similar proportions of MGIB among warfarin and dabigatran recipients (8.5% and 6.8%; P = .6). Nearly all cancers were colorectal or gastric, except for one case each of ampullary cancer, renal cell carcinoma, and melanoma that had metastasized to the luminal gastrointestinal tract. Colorectal cancer accounted for 80% of cancer-related MGIB overall, including 88% in the dabigatran group and 50% in the warfarin group (P = .02). Conversely, warfarin recipients had more MGIB associated with gastric cancer (50%) than did dabigatran recipients (2.9%; P = .001).
Short-term outcomes of MGIB associated with cancer did not vary by anticoagulant, the investigators said. There were no deaths, but two (4.5%) MGIB events required emergency endoscopic treatment, one (2.3%) required emergency surgery, and 33 (75%) required at least one red blood cell transfusion. Compared with patients whose MGIB was unrelated to cancer, those with cancer were more likely to bleed for more than 7 days (27.3% vs. 63.6%; P less than .001). Patients with occult cancer also developed MGIB sooner after starting anticoagulation (223 vs. 343 days; P = .003), but time to bleeding did not significantly vary by type of anticoagulant.
“Most prior studies on cancer bleeding have been case reports and case series in patients receiving warfarin,” the investigators wrote. “Our study is relevant because of the increasing prevalence of atrial fibrillation and anticoagulation in the aging global population, the increasing prescription of direct oral anticoagulants, and the morbidity, mortality, and complex decision making associated with MGIB and especially cancer-related MGIB in patients receiving anticoagulation therapy.”
The RE-LY trial was sponsored by Boehringer Ingelheim . Dr. Flack reported no conflicts of interest. Senior author James Aisenberg, MD, disclosed advisory board and consulting relationships with Boehringer Ingelheim and Portola Pharmaceuticals. Five other coinvestigators disclosed ties to several pharmaceutical companies, and two coinvestigators reported employment with Boehringer Ingelheim. The other coinvestigators had no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Occult cancers accounted for about 1 in every 12 major gastrointestinal bleeding events among patients receiving warfarin or dabigatran for atrial fibrillation.
Major finding: A total of 44 (8.1%) major gastrointestinal bleeds were associated with occult cancers.Data source: A retrospective analysis of 546 unique major gastrointestinal bleeding events from the Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial.
Disclosures: RE-LY was sponsored by Boehringer Ingleheim. Dr. Flack had no conflicts of interest. Senior author James Aisenberg, MD, disclosed advisory board and consulting relationships with Boehringer Ingelheim and Portola Pharmaceuticals. Five other coinvestigators disclosed ties to several pharmaceutical companies, and two coinvestigators reported employment with Boehringer Ingelheim. The other coinvestigators had no conflicts.
Psyllium cut frequency of abdominal pain in pediatric IBS trial
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Compared with placebo maltodextrin, consuming psyllium fiber significantly reduced the self-reported frequency of abdominal pain in children with irritable bowel syndrome.
Major finding: Children who received psyllium reported an average of 8.2 fewer pain episodes, compared with baseline, while controls reported a mean reduction of 4.1 pain episodes (P = .03).
Data source: A randomized, double-blind trial of 103 children aged 12-18 years of age with irritable bowel syndrome.
Disclosures: The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Aggressive HCC in males traced to higher serotonin
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
FROM CELLULAR & MOLECULAR GASTROENTEROLOGY & HEPATOLOGY
Key clinical point: The greater frequency and aggressiveness of hepatocellular carcinoma in men than in women might be attributable to greater synthesis and accumulation of serotonin in males.
Major finding: Serotonin levels were significantly elevated in 7 inflamed, 16 cirrhotic, and 30 cancerous livers, compared with 5 normal livers, among men but not among women.
Data source: Laboratory studies involving a zebrafish model of HCC and tissue samples from 60 human livers.
Disclosures: This study was supported by the National Medical Research Council and the Ministry of Education of Singapore. Dr. Yang and her associates reported no relevant financial disclosures.
Open-capsule PPIs linked to faster ulcer healing after Roux-en-Y
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed ulcers at the gastrojejunal anastomosis after Roux-en-Y gastric bypass.
Major finding: The median time to ulcer healing was 91.0 versus 342.0 days for the open- and closed-capsule groups, respectively (P less than .001).
Data source: A single-center retrospective study of 162 patients.
Disclosures: The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
VIDEO: Point-of-care assay caught acetaminophen toxicity
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point:
Major finding: Compared with etiologic diagnosis, its sensitivity was 100%, specificity was 86%, positive predictive value was 89%, and negative predictive value was 100%.
Data source: Competitive immunoassays of serum samples from 19 healthy controls, 29 patients with nonacetaminophen acute liver failure, and 33 patients with acetaminophen-induced acute liver failure.
Disclosures: The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
AGA Clinical Practice Update: Using FLIP to assess upper GI tract still murky territory
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Clinical Practice Update: Best practice advice on EBT use released
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
FROM GASTROENTEROLOGY